Catherine Bowes Rickman
George and Geneva Boguslavsky Distinguished Professor of Eye Research
The Pathobiology of Age-related Macular Degeneration:
We are interested in the molecular mechanisms underlying the development of age-related macular degeneration (AMD). Currently our studies are focused on development and studies of animal models of AMD, AMD pathogenesis and pre-clinical studies of novel therapies for AMD.
AMD is a late-onset, progressive, neurodegenerative disease with devastating impact on the elderly. This disease occurs primarily in people over the age of 65 years and accounts for approximately 50% of registered blindness in Western Europe and North America. AMD develops as either dry (atrophic) or wet (exudative). AMD is characterized by the accumulation of extracellular lipid- and protein-rich deposits between the retinal pigment epithelium (RPE) and Bruch’s membrane (BrM). These sub-RPE deposits may be focal (drusen) or diffuse and likely contribute to disease pathogenesis and progression similar to intercellular deposits characteristic of other diseases like Alzheimer’s disease, atherosclerosis, and glomerulonephritis. Although the molecular bases of these diseases may be diverse, their pathogenic deposits contain many shared constituents that are attributable, in part, to local inflammation and activation of the complement cascade.
Support for complement in AMD pathogenesis comes from studies implicating variations in the complement factor H (CFH) gene as a strong genetic factor associated with risk for AMD. The precise mechanisms of complement system dysregulation in AMD are unknown, although there are several candidate molecules. Among these is amyloid beta (Abeta), a constituent of drusen, and known activator of the complement system. Abeta deposits in drusen are associated with activated complement proteins and cell injury.
Our studies focus on the role of complement activation in the eye, how this contributes to chronic inflammation - a prelude to AMD pathogenesis and progression – and whether Abeta is a trigger of the complement cascade contributing to inflammatory changes, accumulation of protein-rich deposits and RPE damage.
Mouse models of age-related macular degeneration: The AMD mouse models we have developed provide an in vivo means to interrogate the pathogenic contribution of genetic, inflammatory and environmental factors to AMD onset and progression. Our murine models of AMD include:
(1) Human APOE isoform knock-in Mice: We developed a murine model of AMD by combining three of the risk factors for AMD: advanced age, apolipoprotein E isoform expression and exposure to a high-fat, high-cholesterol (HFC) diet that develop pathological features similar to the morphologic hallmarks observed in both dry and wet human AMD. These disease changes include thick diffuse sub-RPE deposits, lipid- and protein-rich drusen-like deposits, thickening of Bruch’s membrane, patchy regions of RPE atrophy overlying photoreceptor degeneration and, in some animals, spontaneous choroidal neovascularization. This resultant phenotype mimics several of the important phenotypic characteristics of AMD in a temporal, non-fully penetrant and non-invasive manner that is analogous to human AMD progression. We are using this model to study the pathobiology of AMD and to develop therapies. Investigation of this model has revealed that lipid transport dysregulation, inflammation and Abeta deposition contribute to the pathogenesis of the retinal changes observed. This led to identification of novel therapeutic targets for AMD that are we are currently analyzing. In fact, our most recent work shows that therapies targeting Abeta can preserve retinal function in these mice. Validation of these therapeutic targets in AMD could lead to a fundamental paradigm shift in the understanding and treatment of AMD.
(2) Human CFH transgenic Mice: We developed a model of AMD susceptibility by generating transgenic mice carrying the full length CFH gene encoding the normal (Tyr402) and risk-associated (His402) human forms of factor H. We are using these animals and functional studies of the human factor H protein to determine the functional consequence of the AMD risk-associated change.
(3) Cfh heterozygous mice: Based on the substantial evidence implicating complement factor H (CFH) in the pathogenesis of AMD we tested the effect of advanced age, exposure to a high-fat, high-cholesterol (HFC) diet and complement factor H deficiency (Cfh knock out) or Cfh haploinsufficiency (Cfh heterozygous). Characterization of these mice established a link between the complement system and lipid pathways by demonstrating that (i) CFH and lipoproteins compete for binding in the sub-RPE extracellular matrix such that decreasing CFH leads to lipoprotein accumulation and sub-RPE deposit formation; and (ii) detrimental complement activation within sub-RPE deposits leads to RPE damage and vision loss. This new understanding of the complicated interactions of CFH in development of AMD-like pathology represents a paradigm shift in our understanding of AMD and paves the way for identifying more targeted therapeutic strategies for AMD.
We are interested in the molecular mechanisms underlying the development of age-related macular degeneration (AMD). Currently our studies are focused on development and studies of animal models of AMD, AMD pathogenesis and pre-clinical studies of novel therapies for AMD.
AMD is a late-onset, progressive, neurodegenerative disease with devastating impact on the elderly. This disease occurs primarily in people over the age of 65 years and accounts for approximately 50% of registered blindness in Western Europe and North America. AMD develops as either dry (atrophic) or wet (exudative). AMD is characterized by the accumulation of extracellular lipid- and protein-rich deposits between the retinal pigment epithelium (RPE) and Bruch’s membrane (BrM). These sub-RPE deposits may be focal (drusen) or diffuse and likely contribute to disease pathogenesis and progression similar to intercellular deposits characteristic of other diseases like Alzheimer’s disease, atherosclerosis, and glomerulonephritis. Although the molecular bases of these diseases may be diverse, their pathogenic deposits contain many shared constituents that are attributable, in part, to local inflammation and activation of the complement cascade.
Support for complement in AMD pathogenesis comes from studies implicating variations in the complement factor H (CFH) gene as a strong genetic factor associated with risk for AMD. The precise mechanisms of complement system dysregulation in AMD are unknown, although there are several candidate molecules. Among these is amyloid beta (Abeta), a constituent of drusen, and known activator of the complement system. Abeta deposits in drusen are associated with activated complement proteins and cell injury.
Our studies focus on the role of complement activation in the eye, how this contributes to chronic inflammation - a prelude to AMD pathogenesis and progression – and whether Abeta is a trigger of the complement cascade contributing to inflammatory changes, accumulation of protein-rich deposits and RPE damage.
Mouse models of age-related macular degeneration: The AMD mouse models we have developed provide an in vivo means to interrogate the pathogenic contribution of genetic, inflammatory and environmental factors to AMD onset and progression. Our murine models of AMD include:
(1) Human APOE isoform knock-in Mice: We developed a murine model of AMD by combining three of the risk factors for AMD: advanced age, apolipoprotein E isoform expression and exposure to a high-fat, high-cholesterol (HFC) diet that develop pathological features similar to the morphologic hallmarks observed in both dry and wet human AMD. These disease changes include thick diffuse sub-RPE deposits, lipid- and protein-rich drusen-like deposits, thickening of Bruch’s membrane, patchy regions of RPE atrophy overlying photoreceptor degeneration and, in some animals, spontaneous choroidal neovascularization. This resultant phenotype mimics several of the important phenotypic characteristics of AMD in a temporal, non-fully penetrant and non-invasive manner that is analogous to human AMD progression. We are using this model to study the pathobiology of AMD and to develop therapies. Investigation of this model has revealed that lipid transport dysregulation, inflammation and Abeta deposition contribute to the pathogenesis of the retinal changes observed. This led to identification of novel therapeutic targets for AMD that are we are currently analyzing. In fact, our most recent work shows that therapies targeting Abeta can preserve retinal function in these mice. Validation of these therapeutic targets in AMD could lead to a fundamental paradigm shift in the understanding and treatment of AMD.
(2) Human CFH transgenic Mice: We developed a model of AMD susceptibility by generating transgenic mice carrying the full length CFH gene encoding the normal (Tyr402) and risk-associated (His402) human forms of factor H. We are using these animals and functional studies of the human factor H protein to determine the functional consequence of the AMD risk-associated change.
(3) Cfh heterozygous mice: Based on the substantial evidence implicating complement factor H (CFH) in the pathogenesis of AMD we tested the effect of advanced age, exposure to a high-fat, high-cholesterol (HFC) diet and complement factor H deficiency (Cfh knock out) or Cfh haploinsufficiency (Cfh heterozygous). Characterization of these mice established a link between the complement system and lipid pathways by demonstrating that (i) CFH and lipoproteins compete for binding in the sub-RPE extracellular matrix such that decreasing CFH leads to lipoprotein accumulation and sub-RPE deposit formation; and (ii) detrimental complement activation within sub-RPE deposits leads to RPE damage and vision loss. This new understanding of the complicated interactions of CFH in development of AMD-like pathology represents a paradigm shift in our understanding of AMD and paves the way for identifying more targeted therapeutic strategies for AMD.
Current Appointments & Affiliations
- George and Geneva Boguslavsky Distinguished Professor of Eye Research, Ophthalmology, Vitreoretinal Diseases & Surgery, Ophthalmology 2021
- Professor of Ophthalmology, Ophthalmology, Vitreoretinal Diseases & Surgery, Ophthalmology 2018
- Professor in Cell Biology, Cell Biology, Basic Science Departments 2020
Contact Information
- 5010 Albert Eye Research Institute, Durham, NC 27710
- Box 3802 Med Ctr, Durham, NC 27710
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bowes007@duke.edu
(919) 668-0648
- Background
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Education, Training, & Certifications
- Associate Faculty, Ophthalmology, University of Iowa 1997 - 2000
- Postdoctoral Fellow, Jules Stein Eye Institute, University of California - Los Angeles 1990 - 1993
- Ph.D., University of California - Los Angeles 1989
- B.A., University of California - Los Angeles 1983
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Previous Appointments & Affiliations
- Associate Professor in Cell Biology, Cell Biology, Basic Science Departments 2008 - 2020
- Associate Professor of Ophthalmology, Ophthalmology, Vitreoretinal Diseases & Surgery, Ophthalmology 2012 - 2018
- Associate Professor of Ophthalmology, Ophthalmology, Clinical Science Departments 2008 - 2012
- Assistant Professor of Ophthalmology, Ophthalmology, Clinical Science Departments 2000 - 2008
- Assistant Professor in Cell Biology, Cell Biology, Basic Science Departments 2001 - 2008
- Instructor, Temporary in the Department of Ophthalmology, Ophthalmology, Clinical Science Departments 2000
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Academic Positions Outside Duke
- Assistant Professor, Saint Louis University. 1994 - 1997
- Recognition
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In the News
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JUN 28, 2021
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- Expertise
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Subject Headings
- Aged, 80 and over
- Aging
- Alleles
- Alzheimer Disease
- Amyloid Precursor Protein Secretases
- Amyloid beta-Peptides
- Antibodies, Bispecific
- Antigens
- Apolipoprotein E4
- Apolipoproteins E
- Atrophy
- Blotting, Northern
- Blotting, Western
- Cell Death
- Cell Survival
- Cholesterol
- Choroid
- Choroidal Neovascularization
- Complement
- Complement System Proteins
- Dietary Fats
- Disease Models, Animal
- Dose-Response Relationship, Immunologic
- Electroretinography
- Eye
- Eye Diseases
- Eye Proteins
- Gene Expression
- Gene Expression Profiling
- Gene Library
- Genetic Predisposition to Disease
- Genotype
- Glycoproteins
- Immunohistochemistry
- Immunotherapy
- Lipofuscin
- Lipoproteins
- Lysosomes
- Macular Degeneration
- Mice
- Mice, Knockout
- Mice, Mutant Strains
- Mice, Transgenic
- Microarray Analysis
- Microscopy, Electron
- Microscopy, Fluorescence
- Multifactorial Inheritance
- Neurodegenerative Diseases
- Oligonucleotide Array Sequence Analysis
- Oxidative Stress
- Phenotype
- Photoreceptor Cells
- Pigment Epithelium of Eye
- Polymorphism, Single Nucleotide
- Proteins
- Reactive Oxygen Species
- Retina
- Retinal Cone Photoreceptor Cells
- Retinal Degeneration
- Retinal Diseases
- Retinal Pigment Epithelium
- Sclera
- Vascular Endothelial Growth Factor A
- Vision, Ocular
- Visual Acuity
- Research
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Selected Grants
- Medical Scientist Training Program awarded by National Institutes of Health 2022 - 2027
- Training Program in Developmental and Stem Cell Biology awarded by National Institutes of Health 2001 - 2027
- Complement factor H modulates lipoprotein clearance in AMD awarded by National Institutes of Health 2020 - 2025
- Genetic and Genomics Training Grant awarded by National Institutes of Health 2020 - 2025
- RPE Exosomes in Age-related Macular Degeneration awarded by National Institutes of Health 2022 - 2025
- Preclinical Testing of Complement Factor H Gene Augmentation Therapy to Treat Dry AMD awarded by Foundation Fighting Blindness, Inc 2022 - 2025
- Cellular and Molecular Dynamics of Retinal Microglial in the Context of Photoreceptor Degeneration awarded by National Institutes of Health 2020 - 2024
- The Role of RPE-derived Exosomes in Deposit Formation and ECM Modulation awarded by National Institutes of Health 2021 - 2022
- RPE Trophic Activity for Retinal Protection awarded by University of Arizona 2017 - 2022
- HDL - a therapeutic target for age related macular degeneration. awarded by Edward N. & Della L. Thome Memorial Foundation 2019 - 2021
- Prevention of Early/Intermediate AMD using Anti-C5 Immunotherapy awarded by Research To Prevent Blindness, Inc. 2018 - 2020
- Dose range finding study for AAV8.CBA.humanFH vectors in CFH-deficient Mice awarded by Aevitas Therapeutics, Inc. 2019 - 2020
- Genetics Training Grant awarded by National Institutes of Health 1979 - 2020
- Testing the effect of a CFH agonistic monoclonal PEG-Fab awarded by Gemini Therapeutics 2020
- Innate immunity, lipoproteins and AMD progression awarded by National Institutes of Health 2016 - 2019
- Gemini Therapeutics, Inc.- SRA awarded by Gemini Therapeutics 2018
- The Role of Exosomes in Dry AMD awarded by BrightFocus Foundation 2015 - 2018
- Regulation of Sub-RPE Deposit Formation in AMD by Local and Systemic Complement Factor H awarded by Foundation Fighting Blindness, Inc 2015 - 2018
- Immunohistochemistry (IHC) of Photothermal and Photomechanical Laser Lesions in the Retina to Support the BSELL Project awarded by TASC, Inc. 2015 - 2016
- Targeting Amyloid beta for the treatment of dry Age-related Macular Degeneration awarded by F. Hoffmann-La Roche Ltd 2015
- Ocular Pharmacology and Therapeutics Conference awarded by National Institutes of Health 2014 - 2015
- Complement and Pathogenic Mechanisms of AMD awarded by National Institutes of Health 2009 - 2015
- A non-canonical role for b-secretase in AMD awarded by The Trustees of Indiana University 2013 - 2014
- Candidate Genes for Primary Open Angle Glaucoma awarded by National Institutes of Health 2007 - 2012
- The Molecular Basis of Pseudoexfoliation Syndrome awarded by National Institutes of Health 2003 - 2009
- Proteome Map of the Photoreceptor Cell awarded by National Institutes of Health 2006 - 2009
- Murine AMD Model Based on Constellation of Known Human AMD Risk Factors awarded by National Institutes of Health 2006 - 2008
- Characterization of Genes in Normal and AMD Retinas awarded by National Institutes of Health 1995 - 2006
- Characterization of Genes in Normal and AMD Retinas awarded by National Institutes of Health 1995 - 2001
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External Relationships
- 4D Molecular Therapeutics
- Aerie Pharmaceuticals, Inc.
- Aevitas Therapeutics, Inc., a subsidiary of Fortress Biotech, Inc.
- Biogen
- Biospark Intellectual Property Law
- Character Biosciences
- Publications & Artistic Works
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Selected Publications
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Books
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Ash JD, Anderson RE, LaVail MM, Rickman CB, Hollyfield JG, Grimm C. Preface. Vol. 1074. 2018.
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Academic Articles
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Landowski M, Grindel S, Hao Y, Ikeda S, Bowes Rickman C, Ikeda A. A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration. J Vis Exp. 2023 Mar 10;(193).Full Text Link to Item
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Xu L, Ruddick WN, Bolch SN, Klingeborn M, Dyka FM, Kulkarni MM, et al. Distinct Phenotypic Consequences of Pathogenic Mutants Associated with Late-Onset Retinal Degeneration. Am J Pathol. 2022 Oct 31;Full Text Link to Item
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Bharti K, den Hollander AI, Lakkaraju A, Sinha D, Williams DS, Finnemann SC, et al. Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration. Exp Eye Res. 2022 Sep;222:109170.Full Text Link to Item
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Whitley JA, Kim S, Lou L, Ye C, Alsaidan OA, Sulejmani E, et al. Encapsulating Cas9 into extracellular vesicles by protein myristoylation. J Extracell Vesicles. 2022 Apr;11(4):e12196.Full Text Link to Item
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Landowski M, Bowes Rickman C. Targeting Lipid Metabolism for the Treatment of Age-Related Macular Degeneration: Insights from Preclinical Mouse Models. J Ocul Pharmacol Ther. 2022;38(1):3–32.Full Text Open Access Copy Link to Item
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Kelly UL, Grigsby D, Cady MA, Landowski M, Skiba NP, Liu J, et al. High-density lipoproteins are a potential therapeutic target for age-related macular degeneration. J Biol Chem. 2020 Sep 25;295(39):13601–16.Full Text Link to Item
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Handa JT, Bowes Rickman C, Dick AD, Gorin MB, Miller JW, Toth CA, et al. A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration. Nat Commun. 2019 Jul 26;10(1):3347.Full Text Link to Item
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O’Koren EG, Yu C, Klingeborn M, Wong AYW, Prigge CL, Mathew R, et al. Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration. Immunity. 2019 Mar 19;50(3):723-737.e7.Full Text Link to Item
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Landowski M, Kelly U, Klingeborn M, Groelle M, Ding J-D, Grigsby D, et al. Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice. Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3703–11.Full Text Link to Item
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Rickman CB, Grimm C, Anderson RE, Ash JD, LaVail MM, Hollyfield JG. Correction to: Retinal Degenerative Diseases. Adv Exp Med Biol. 2019;1185:C1.Full Text Link to Item
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Klingeborn M, Skiba NP, Stamer WD, Bowes Rickman C. Isolation of Retinal Exosome Biomarkers from Blood by Targeted Immunocapture. Adv Exp Med Biol. 2019;1185:21–5.Full Text Link to Item
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Klingeborn M, Dismuke WM, Skiba NP, Kelly U, Stamer WD, Bowes Rickman C. Author Correction: Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers. Sci Rep. 2018 Nov 20;8(1):17327.Full Text Link to Item
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Toomey CB, Landowski M, Klingeborn M, Kelly U, Deans J, Dong H, et al. Effect of Anti-C5a Therapy in a Murine Model of Early/Intermediate Dry Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):662–73.Full Text Link to Item
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Klingeborn M, Stamer WD, Bowes Rickman C. Polarized Exosome Release from the Retinal Pigmented Epithelium. Adv Exp Med Biol. 2018;1074:539–44.Full Text Link to Item
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Toomey CB, Johnson LV, Bowes Rickman C. Complement factor H in AMD: Bridging genetic associations and pathobiology. Prog Retin Eye Res. 2018 Jan;62:38–57.Full Text Link to Item
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Klingeborn M, Dismuke WM, Skiba NP, Kelly U, Stamer WD, Bowes Rickman C. Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers. Sci Rep. 2017 Jul 7;7(1):4901.Full Text Open Access Copy Link to Item
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Klingeborn M, Dismuke WM, Bowes Rickman C, Stamer WD. Roles of exosomes in the normal and diseased eye. Prog Retin Eye Res. 2017 Jul;59:158–77.Full Text Link to Item
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Carver KA, Lin CM, Bowes Rickman C, Yang D. Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD. Biochem Biophys Res Commun. 2017 Jan 1;482(1):81–6.Full Text Link to Item
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Song C, Mitter SK, Qi X, Beli E, Rao HV, Ding J, et al. Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy. Plos One. 2017;12(2):e0171940.Full Text Link to Item
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Tan PL, Bowes Rickman C, Katsanis N. AMD and the alternative complement pathway: genetics and functional implications. Hum Genomics. 2016 Jun 21;10(1):23.Full Text Link to Item
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Toomey CB, Kelly U, Saban DR, Bowes Rickman C. Regulation of age-related macular degeneration-like pathology by complement factor H. Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):E3040–9.Full Text Link to Item
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Ding J-D, Kelly U, Landowski M, Toomey CB, Groelle M, Miller C, et al. Expression of human complement factor H prevents age-related macular degeneration-like retina damage and kidney abnormalities in aged Cfh knockout mice. Am J Pathol. 2015 Jan;185(1):29–42.Full Text Link to Item
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Mitter SK, Song C, Qi X, Mao H, Rao H, Akin D, et al. Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD. Autophagy. 2014;10(11):1989–2005.Full Text Link to Item
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Ding J-D, Kelly U, Groelle M, Christenbury JG, Zhang W, Bowes Rickman C. The role of complement dysregulation in AMD mouse models. Adv Exp Med Biol. 2014;801:213–9.Full Text Link to Item
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Bowes Rickman C, Farsiu S, Toth CA, Klingeborn M. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging. Invest Ophthalmol Vis Sci. 2013 Dec 13;54(14):ORSF68–80.Full Text Link to Item
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Cai J, Qi X, Kociok N, Skosyrski S, Emilio A, Ruan Q, et al. β-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment. Embo Mol Med. 2012 Sep;4(9):980–91.Full Text Link to Item
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Chiu SJ, Toth CA, Bowes Rickman C, Izatt JA, Farsiu S. Automatic segmentation of closed-contour features in ophthalmic images using graph theory and dynamic programming. Biomed Opt Express. 2012 May 1;3(5):1127–40.Full Text Link to Item
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Trotter JH, Klein M, Jinwal UK, Abisambra JF, Dickey CA, Tharkur J, et al. ApoER2 function in the establishment and maintenance of retinal synaptic connectivity. J Neurosci. 2011 Oct 5;31(40):14413–23.Full Text Link to Item
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Ding J-D, Johnson LV, Herrmann R, Farsiu S, Smith SG, Groelle M, et al. Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):E279–87.Full Text Link to Item
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Liu Y, Munro D, Layfield D, Dellinger A, Walter J, Peterson K, et al. Serial analysis of gene expression (SAGE) in normal human trabecular meshwork. Mol Vis. 2011 Apr 8;17:885–93.Link to Item
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Kelly U, Yu L, Kumar P, Ding J-D, Jiang H, Hageman GS, et al. Heparan sulfate, including that in Bruch's membrane, inhibits the complement alternative pathway: implications for age-related macular degeneration. J Immunol. 2010 Nov 1;185(9):5486–94.Full Text Link to Item
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Anderson DH, Radeke MJ, Gallo NB, Chapin EA, Johnson PT, Curletti CR, et al. The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res. 2010 Mar;29(2):95–112.Full Text Link to Item
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Brown NH, Koreishi AF, McCall M, Izatt JA, Rickman CB, Toth CA. Developing SDOCT to assess donor human eyes prior to tissue sectioning for research. Graefes Arch Clin Exp Ophthalmol. 2009 Aug;247(8):1069–80.Full Text Link to Item
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Kelly U, Rickman CB, Postel EA, Hauser MA, Hageman GS, Arshavsky VY, et al. Rapid and sensitive method for detection of Y402, H402, I62, and V62 variants of complement factor H in human plasma samples using mass spectrometry. Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1540–5.Full Text Link to Item
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Metlapally R, Michaelides M, Bulusu A, Li Y-J, Schwartz M, Rosenberg T, et al. Evaluation of the X-linked high-grade myopia locus (MYP1) with cone dysfunction and color vision deficiencies. Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1552–8.Full Text Link to Item
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Swaroop A, Chew EY, Rickman CB, Abecasis GR. Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. Annu Rev Genomics Hum Genet. 2009;10:19–43.Full Text Link to Item
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Wistow G, Peterson K, Gao J, Buchoff P, Jaworski C, Bowes-Rickman C, et al. NEIBank: genomics and bioinformatics resources for vision research. Mol Vis. 2008 Jul 18;14:1327–37.Link to Item
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Ding J-D, Lin J, Mace BE, Herrmann R, Sullivan P, Bowes Rickman C. Targeting age-related macular degeneration with Alzheimer's disease based immunotherapies: anti-amyloid-beta antibody attenuates pathologies in an age-related macular degeneration mouse model. Vision Res. 2008 Feb;48(3):339–45.Full Text Link to Item
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Malek G, Jamison JA, Mace B, Sullivan P, Rickman CB. ERG responses and microarray analysis of gene expression in a multifactorial murine model of age-related retinal degeneration. Adv Exp Med Biol. 2008;613:165–70.Full Text Link to Item
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Yu L, Kelly U, Ebright JN, Malek G, Saloupis P, Rickman DW, et al. Oxidative stress-induced expression and modulation of Phosphatase of Regenerating Liver-1 (PRL-1) in mammalian retina. Biochim Biophys Acta. 2007 Sep;1773(9):1473–82.Full Text Link to Item
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Bowne SJ, Liu Q, Sullivan LS, Zhu J, Spellicy CJ, Rickman CB, et al. Why do mutations in the ubiquitously expressed housekeeping gene IMPDH1 cause retina-specific photoreceptor degeneration? Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3754–65.Full Text Link to Item
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Bowes Rickman C, Ebright JN, Zavodni ZJ, Yu L, Wang T, Daiger SP, et al. Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE. Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2305–16.Full Text Link to Item
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Rosenthal R, Malek G, Salomon N, Peill-Meininghaus M, Coeppicus L, Wohlleben H, et al. The fibroblast growth factor receptors, FGFR-1 and FGFR-2, mediate two independent signalling pathways in human retinal pigment epithelial cells. Biochem Biophys Res Commun. 2005 Nov 11;337(1):241–7.Full Text Link to Item
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Malek G, Johnson LV, Mace BE, Saloupis P, Schmechel DE, Rickman DW, et al. Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration. Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11900–5.Full Text Link to Item
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Cahill MT, Mruthyunjaya P, Bowes Rickman C, Toth CA. Recurrence of retinal pigment epithelial changes after macular translocation with 360 degrees peripheral retinectomy for geographic atrophy. Arch Ophthalmol. 2005 Jul;123(7):935–8.Full Text Link to Item
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Yang P, Wiser JL, Peairs JJ, Ebright JN, Zavodni ZJ, Bowes Rickman C, et al. Human RPE expression of cell survival factors. Invest Ophthalmol Vis Sci. 2005 May;46(5):1755–64.Full Text Link to Item
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Rosenthal R, Wohlleben H, Malek G, Schlichting L, Thieme H, Bowes Rickman C, et al. Insulin-like growth factor-1 contributes to neovascularization in age-related macular degeneration. Biochem Biophys Res Commun. 2004 Oct 29;323(4):1203–8.Full Text Link to Item
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Thompson CL, Bowes Rickman C, Shaw SJ, Ebright JN, Kelly U, Sancar A, et al. Expression of the blue-light receptor cryptochrome in the human retina. Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4515–21.Full Text Link to Item
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Yarovinsky TO, Rickman DW, Diamond RH, Taub R, Hageman GS, Bowes Rickman C. Expression of the protein tyrosine phosphatase, phosphatase of regenerating liver 1, in the outer segments of primate cone photoreceptors. Brain Res Mol Brain Res. 2000 Apr 14;77(1):95–103.Full Text Link to Item
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Rickman DW, Nacke RE, Bowes Rickman C. Characterization of the cell death promoter, Bad, in the developing rat retina and forebrain. Brain Res Dev Brain Res. 1999 Jun 8;115(1):41–7.Full Text Link to Item
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Rickman DW, Bowes Rickman C. Suppression of trkB expression by antisense oligonucleotides alters a neuronal phenotype in the rod pathway of the developing rat retina. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12564–9.Full Text Link to Item
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Di Polo A, Bowes Rickman C, Farber DB. Isolation and initial characterization of the 5' flanking region of the human and murine cyclic guanosine monophosphate-phosphodiesterase beta-subunit genes. Invest Ophthalmol Vis Sci. 1996 Mar;37(4):551–60.Link to Item
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Kozak CA, Danciger M, Bowes C, Adamson MC, Palczewski K, Polans AS, et al. Localization of three genes expressed in retina on mouse chromosome 11. Mamm Genome. 1995 Feb;6(2):142–4.Full Text Link to Item
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Bowes C, Li T, Frankel WN, Danciger M, Coffin JM, Applebury ML, et al. Localization of a retroviral element within the rd gene coding for the beta subunit of cGMP phosphodiesterase. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2955–9.Full Text Link to Item
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Bateman JB, Klisak I, Kojis T, Mohandas T, Sparkes RS, Li TS, et al. Assignment of the beta-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse rd gene) to human chromosome 4p16. Genomics. 1992 Mar;12(3):601–3.Full Text Link to Item
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Klumpp DJ, Farber DB, Bowes C, Song EJ, Pinto LH. The potassium channel MBK1 (Kv1.1) is expressed in the mouse retina. Cell Mol Neurobiol. 1991 Dec;11(6):611–22.Full Text Link to Item
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Bowes C, Li T, Danciger M, Baxter LC, Applebury ML, Farber DB. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature. 1990 Oct 18;347(6294):677–80.Full Text Link to Item
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Danciger M, Bowes C, Kozak CA, LaVail MM, Farber DB. Fine mapping of a putative rd cDNA and its co-segregation with rd expression. Invest Ophthalmol Vis Sci. 1990 Aug;31(8):1427–32.Link to Item
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Bowes C, Danciger M, Kozak CA, Farber DB. Isolation of a candidate cDNA for the gene causing retinal degeneration in the rd mouse. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9722–6.Full Text Link to Item
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Bowes C, van Veen T, Farber DB. Opsin, G-protein and 48-kDa protein in normal and rd mouse retinas: developmental expression of mRNAs and proteins and light/dark cycling of mRNAs. Exp Eye Res. 1988 Sep;47(3):369–90.Full Text Link to Item
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Bowes C, Farber DB. mRNAs coding for proteins of the cGMP cascade in the degenerative retina of the rd mouse. Exp Eye Res. 1987 Oct;45(4):467–80.Full Text Link to Item
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Book Sections
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Qian Q, Mitter SK, Pay SL, Qi X, Rickman CB, Grant MB, et al. A Non-Canonical Role for β-Secretase in the Retina. In 2016. p. 333–9.Full Text Link to Item
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Malek G, Mace B, Saloupis P, Schmechel D, Rickman D, Sullivan P, et al. Initial observations of key features of age-related macular degeneration in APOE targeted replacement mice. In 2006. p. 109–17.Full Text Link to Item
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Farber DB, Flannery JG, Bowes-Rickman C. The rd mouse story: Seventy years of research on an animal model of inherited retinal degeneration. In 1994. p. 31–64.Full Text
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Other Articles
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Berger BB, Gunderson I, Rickman CB, Lin J, Garzone P. An investigational therapy for geographic atrophy in age-related macular degeneration. Vol. MAY-JUNE, Retina Today. 2014. p. 73–5.
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RICKMAN CB, HAGEMAN GS. IDENTIFICATION OF PRIMATE FOVEA-SPECIFIC MESSENGER-RNAS. Vol. 36, Investigative Ophthalmology & Visual Science. LIPPINCOTT-RAVEN PUBL; 1995. p. S621–S621.Link to Item
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RICKMAN DW, RICKMAN CB. SUPPRESSION OF TRKB NEUROTROPHIN RECEPTOR EXPRESSION IN DEVELOPING RETINA BY ANTISENSE OLIGONUCLEOTIDES. Vol. 36, Investigative Ophthalmology & Visual Science. LIPPINCOTT-RAVEN PUBL; 1995. p. S256–S256.Link to Item
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Book Reviews
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Farber DB, Bowes C, Danciger M. Studies leading to the isolation of a cDNA for the gene causing retinal degeneration in the rd mouse. Prog Clin Biol Res. 1991;362:67–86.Link to Item
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Conference Papers
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Hanke-Gogokhia C, Finkelstein S, Klingeborn M, Zapadka T, Rickman CB, Arshavsky VY, et al. Dynamin-1 and-3 are essential for the structure and function of mouse rod photoreceptor synaptic terminals. In: Investigative Ophthalmology & Visual Science. 2022.Link to Item
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Li G, Wilson A, Rickman CB, Stamer WD. Outflow segmentation patterns and pilocarpine induced outflow changes with age. In: Investigative Ophthalmology & Visual Science. 2022.Link to Item
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Hernandez B, Klingeborn M, Skiba N, Grigsby D, Kelly U, Caday M, et al. Chronic Oxidative Stress in Primary Retinal Pigmented Epithelium Monolayers Increases Basolateral Exosome Release and Changes Both Exosome and Extracellular Matrix Proteomes. In: Investigative Ophthalmology & Visual Science. 2021.Link to Item
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Vajzovic L, Sleiman K, Viehland C, Carrasco-Zevallos OM, Klingeborn M, Dandridge A, et al. Four-Dimensional Microscope-Integrated Optical Coherence Tomography Guidance in a Model Eye Subretinal Surgery. In: Retina. 2019. p. S194–8.Full Text Link to Item
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Grigsby D, Landowski M, Kelly U, Klingeborn M, Groelle M, Rickman CB. Systemic AAV delivery of complement regulator, Factor H Like-1 (FHL-1) impacts visual function. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2019.Link to Item
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Figueroa A, Congrove NR, Sillik SA, Sadideen DT, Falk T, Rickman CB, et al. Exosome uptake is selective but not species or tissue-specific. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2018.Link to Item
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Landowski M, Kelly UL, Grigsby D, Groelle M, Rickman CB. Dietary Cholesterol Contributes to Vision Loss in a Complement-Dysregulated AMD Mouse Model. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2018.Link to Item
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Ash JD, Anderson RE, LaVail MM, Rickman CB, Hollyfield JG, Grimm C. Retinal Degenerative Diseases Mechanisms and Experimental Therapy Preface. In: Ash JD, Anderson RE, LaVail MM, Rickman CB, Hollyfield JG, Grimm C, editors. Retinal Degenerative Diseases: Mechanisms and Experimental Therapy. SPRINGER INTERNATIONAL PUBLISHING AG; 2018. p. IX–X.Link to Item
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Kelly UL, Landowski M, Skiba N, Liu J, Rickman CB. Lipoprotein synthesis and deposition in the eye is regulated by the complement system and glycosaminoglycans (GAGs). In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2017.Link to Item
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Klingeborn M, Rickman CB, Stamer WD. The Potential of Ocular Exosomal Biomarkers as Therapeutic Targets, and as Diagnostic and Prognostic Indicators. In: In Vitro Cellular & Developmental Biology Animal. SPRINGER; 2017. p. S9–S9.Link to Item
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Landowski M, Ding J, Klingeborn M, Kelly U, Groelle M, Rickman CB. Effect of Complement Factor H Variants in Regulating AMD-like Pathologies In Vivo. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2016.Link to Item
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Agbaga M-PG, Ding J, Hopiavuori B, Li F, Brush RS, Ayyagari R, et al. Depletion of Very Long Chain Polyunsaturated Fatty Acids Causes Functional and Ultrastructural Changes in Photoreceptors Independent of Mutant ELOVL4 Expression. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2015.Link to Item
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Deans JR, Toomey CB, Kelly U, Klingeborn M, Rickman CB. Complement dysregulation exacerbates AMD-like phenotype in APOE4 transgenic mouse model of AMD. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2015.Link to Item
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Alhatem AH, Lenchik N, Beranova-Giorgianni S, Klingeborn M, New DD, Giorgianni F, et al. The Apolipoprotein E4 Targeted Replacement (APOE4 TR) Mouse Model of Age-Related Macular Degeneration (AMD) Exhibits Anti-Retinal Autoreactivity. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2014.Link to Item
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Landowski MJ, Kelly UL, Groelle M, Ding J, Rickman CB. Exogenous CFH Contributes to Complement Regulation in the Eyes of Cfh-Deficient Animals. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2014.Link to Item
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Ding J, Kelly U, Groelle M, Rickman CB. Human Complement Factor H (CFH) Transgene Expression Rescues the Visual Function and Retina Abnormalities in Aged cfh-/- Mice. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2013.Link to Item
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Singhapricha T, Kelly U, Landowski M, Groelle M, Saloupis P, Rickman CB. Oxidative Stress Significantly Increases Expression of Inflammatory and Antioxidant Markers in Complement Factor H Deficient Mice Compared to Wild-Type Mice. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2013.Link to Item
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Kelly U, Ding J-D, Landowski M, Groelle M, Jiang H, Skiba N, et al. Development of humanized complement factor H transgenic mice to interrogate the effect of age-related macular degeneration risk associated variants in vivo. In: Immunobiology. Elsevier BV; 2012. p. 1164–1164.Full Text
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Malek G, Mace B, Saloupis P, Schmechel D, Rickman D, Sullivan P, et al. Initial observations of key features of age-related macular degeneration in APOE targeted replacement mice - For contributed volumes. In: Retinal Degenerative Diseases. 2006. p. 109–17.Link to Item
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Bowne SJ, Sullivan LS, Zhu J, Liu Q, Pierce EA, Ebright JN, et al. Why do mutations in a widely expressed gene, IMPDH1, cause autosomal dominant retinitis pigmentosa? In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Ebright JN, Boon K, Hauser MA, Daiger SP, Rickman CB. Using the human retina and RPE transcriptomes to identify candidate disease genes for retinal dystrophies. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Kelly UL, Yu L, McKay BS, Rickman CB. Characterization of the cone photoreceptor-associated protein, FASH3B. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Malek G, Saloupis P, Mace B, Schmechel D, Rickman D, Sullivan P, et al. Characterization of the natural history of neovascularization and basal deposits in a non-invasive murine model of age-related macular degeneration. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Peairs JJ, Yang P, Zavodni ZJ, Ebright JN, Rickman CB, Jaffe GJ. Human RPE cell survival factor gene expression in situ compared to expression in vitro. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Walsh MM, Malek G, Saloupis P, Sullivan PM, Mace B, Schmechel DE, et al. Apolipoprotein (APOE) allelic expression, advanced age, and diet contribute to atrophic degenerative changes in retinal ganglion cells and optic nerve in a mouse model: Predictors of severity of glaucoma? In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Yu L, Kelly U, Ebright JN, Malek G, McKay BS, Rickman CB. Light dependent membrane association of PRL-1, a phosphatase expressed in cone photoreceptors. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Zavodni ZJ, Ebright JN, Malek G, Storms RW, Rickman CB. Challenges of human RPE gene profiling. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2005.Link to Item
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Malek G, Saloupis P, Mace B, Schmechel D, Sullivan P, Rickman CB. Murine choroidal neovascularization: A model for exudative age-related macular degeneration (AMD). In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2004. p. U731–U731.Link to Item
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Pericak-Vance MA, Schmidt S, Scott WK, Hauser ER, Postel EA, Agarwal A, et al. Ordered subsets linkage analysis and expression profiling of chromosome 16p in age-related macular degeneration. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2004. p. U992–U992.Link to Item
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Rickman CB, Ebright JN, Boon K. Human cone-enriched macular retina expression profiles. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2004. p. U320–U320.Link to Item
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Saghizadeh M, Akhmedov NB, Yeung E, Rickman CB, Aguirre GD, Nelson SF, et al. Identification of genes expressed in cone photoreceptor cells. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2004. p. U320–U320.Link to Item
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Schmidt S, Scott WK, Fan YT, Postel EA, Agarwal A, Gass JDM, et al. Analysis of nitric oxide synthase genes in age-related macular degeneration. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2004. p. U992–U992.Link to Item
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Wiser JL, Ebright JN, Rickman CB, Jaffe GJ. SRF exposure up-regulates cytokine and anti-apoptotic factor expression in cultured human RPE cells. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2004. p. U479–U479.Link to Item
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Yu L, Kelly U, Ebright JN, Malek G, McKay BS, Rickman CB. Characterization of PRL-1, a human cone photoreceptor protein tyrosine phosphatase. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2004. p. U529–U529.Link to Item
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Schmidt S, Postell EA, Agarwal A, Gilbert JR, Gorin MB, Rickman CB, et al. Using genomic convergence to identify susceptibility genes for age-related macular degeneration (AMD). In: American Journal of Human Genetics. UNIV CHICAGO PRESS; 2003. p. 494–494.Link to Item
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Malek G, Sullivan PM, Mace BE, Schmechel D, Rickman CB. Effect of diet and targeted replacement human APOE isoforms in aged mice. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2003. p. U405–U405.Link to Item
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Rickman CB, Ebright J, Rho S. Macular transcription profiles and single cell RT-PCR evaluation of candidate genes for inherited macular- and cone-rod dystrophies. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2003. p. U387–U387.Link to Item
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Rickman CB, Sullivan PM, Mace BE, Rickman DW. Targeted replacement of human ApoE Isoforms in aged mice: Risk factors for retinal degeneration? In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2002. p. U151–U151.Link to Item
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Challa P, Gonzalez P, Allingham RR, Epstein DL, Rickman CB. Identification of genes differentially expressed in individuals with pseudoexfoliation syndrome. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2002. p. U1157–U1157.Link to Item
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Rickman CB, McKay BS, Yarovinsky TO, Rickman DW. Analysis of proteins encoded by two fovea-associated candidate genes for macular dystrophies. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2001. p. S770–S770.Link to Item
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Rickman DW, Yarovinsky TO, Trasarti L, Rickman CB. Rod bipolar cells of the mammalian retina express the protein tyrosine phosphatase, PRL-1. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 2000. p. S878–S878.Link to Item
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Rickman DW, Nacke RE, Rickman CB. Characterization of the cell death promoter, Bad, in the developing rat retina and forebrain. In: Investigative Ophthalmology & Visual Science. ASSOC RESEARCH VISION OPHTHALMOLOGY INC; 1999. p. S161–S161.Link to Item
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Franklin AJ, Kuehn MH, Warner RB, Thompsen J, Russell SR, Rickman CB, et al. Evaluation of differentially-expressed rpe gene transcripts as candidates for age-related macular degeneration. In: Investigative Ophthalmology & Visual Science. LIPPINCOTT-RAVEN PUBL; 1997. p. 1640–1640.Link to Item
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