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Daniel Raphael Saban

Professor of Ophthalmology
Ophthalmology, Corneal Diseases

Selected Publications


The Yin and Yang of non-immune and immune responses in meibomian gland dysfunction.

Journal Article Ocul Surf · April 2024 Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meib ... Full text Link to item Cite

Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2.

Journal Article J Exp Med · March 4, 2024 Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and nic ... Full text Link to item Cite

An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2.

Journal Article Nat Commun · October 21, 2023 Granulomas often form around pathogens that cause chronic infections. Here, we discover an innate granuloma model in mice with an environmental bacterium called Chromobacterium violaceum. Granuloma formation not only successfully walls off, but also clears ... Full text Link to item Cite

Meibomian Gland Dysfunction: A Route of Ocular Graft-Versus-Host Disease Progression That Drives a Vicious Cycle of Ocular Surface Inflammatory Damage.

Journal Article Am J Ophthalmol · March 2023 PURPOSE: To investigate the role of aggressive meibomian gland dysfunction (MGD) in the immune pathogenesis of ocular graft-vs-host disease (GVHD). METHODS: In mice, an allogeneic GVHD model was established by transferring bone marrow (BM) and purified spl ... Full text Link to item Cite

Microglia Preserve Visual Function in a Mouse Model of Retinitis Pigmentosa with Rhodopsin-P23H Mutant.

Journal Article Adv Exp Med Biol · 2023 Most forms of outer retinal degenerative diseases involve the ectopic accumulation of microglia/macrophages in the subretinal space, including retinitis pigmentosa. However, their role in the loss of photoreceptor function during retinal degeneration remai ... Full text Link to item Cite

Microglia Drive Pockets of Neuroinflammation in Middle Age.

Journal Article J Neurosci · May 11, 2022 During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and ot ... Full text Link to item Cite

Allergy and Immune-Mediated Tissue Injury

Chapter · January 1, 2022 The immune system serves a protective role in our defense against pathogens. However, the immune response may sometimes be misdirected or exaggerated in a way that results in pathology. Such inappropriate responses are termed as "hypersensitivity reactions ... Full text Cite

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.

Journal Article Transplant Cell Ther · October 2021 Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Pro ... Full text Link to item Cite

Meibomian gland dysfunction is suppressed via selective inhibition of immune responses by topical LFA-1/ICAM antagonism with lifitegrast in the allergic eye disease (AED) model.

Journal Article Ocul Surf · July 2021 PURPOSE: The etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meib ... Full text Link to item Cite

Mucosal-associated invariant T cell responses differ by sex in COVID-19.

Journal Article Med · June 11, 2021 BACKGROUND: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood. METHODS: We carried out sex-balanced sampling of peripheral blood mon ... Full text Open Access Link to item Cite

BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.

Journal Article Blood · May 6, 2021 Patients with chronic graft-versus-host disease (cGVHD) have increased B cell-activating factor (BAFF) levels, but whether BAFF promotes disease after allogeneic bone marrow transplantation (allo-BMT) remains unknown. In a major histocompatibility complex- ... Full text Link to item Cite

In vivo quantitative analysis of anterior chamber white blood cell mixture composition using spectroscopic optical coherence tomography.

Journal Article Biomed Opt Express · April 1, 2021 Anterior uveitis is the most common form of intraocular inflammation, and one of its main signs is the presence of white blood cells (WBCs) in the anterior chamber (AC). Clinically, the true composition of cells can currently only be obtained using AC para ... Full text Link to item Cite

The cornea IV immunology, infection, neovascularization, and surgery chapter 1: Corneal immunology.

Journal Article Exp Eye Res · April 2021 PURPOSE: of Review: This review offers an informed and up-to-date insight on the immune profile of the cornea and the factors that govern the regulation of such a unique immune environment. SUMMARY: The cornea is a unique tissue that performs the specializ ... Full text Link to item Cite

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

Journal Article Nat Commun · February 17, 2021 SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral bloo ... Full text Open Access Link to item Cite

Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy.

Journal Article Int J Mol Sci · October 12, 2020 Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse mo ... Full text Link to item Cite

Microglia versus Monocytes: Distinct Roles in Degenerative Diseases of the Retina.

Journal Article Trends Neurosci · June 2020 Unlike in the healthy mammalian retina, macrophages in retinal degenerative states are not solely comprised of microglia but may include monocyte-derived recruits. Recent studies have applied transgenics, lineage-tracing, and transcriptomics to help deciph ... Full text Link to item Cite

The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options.

Journal Article J Ocul Pharmacol Ther · April 2020 Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the bal ... Full text Link to item Cite

scDAPA: detection and visualization of dynamic alternative polyadenylation from single cell RNA-seq data.

Journal Article Bioinformatics · February 15, 2020 Featured Publication MOTIVATION: Alternative polyadenylation (APA) plays a key post-transcriptional regulatory role in mRNA stability and functions in eukaryotes. Single cell RNA-seq (scRNA-seq) is a powerful tool to discover cellular heterogeneity at gene expression level. Gi ... Full text Link to item Cite

Neutrophil L-Plastin Controls Ocular Paucibacteriality and Susceptibility to Keratitis.

Journal Article Front Immunol · 2020 Why ocular mucosa is paucibacterial is unknown. Many different mechanisms have been suggested but the comprehensive experimental studies are sparse. We found that a deficiency in L-plastin (LCP1), an actin bundling protein, resulted in an ocular commensal ... Full text Link to item Cite

The Yin and Yang of non-immune and immune responses in meibomian gland dysfunction.

Journal Article Ocul Surf · April 2024 Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meib ... Full text Link to item Cite

Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2.

Journal Article J Exp Med · March 4, 2024 Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and nic ... Full text Link to item Cite

An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2.

Journal Article Nat Commun · October 21, 2023 Granulomas often form around pathogens that cause chronic infections. Here, we discover an innate granuloma model in mice with an environmental bacterium called Chromobacterium violaceum. Granuloma formation not only successfully walls off, but also clears ... Full text Link to item Cite

Meibomian Gland Dysfunction: A Route of Ocular Graft-Versus-Host Disease Progression That Drives a Vicious Cycle of Ocular Surface Inflammatory Damage.

Journal Article Am J Ophthalmol · March 2023 PURPOSE: To investigate the role of aggressive meibomian gland dysfunction (MGD) in the immune pathogenesis of ocular graft-vs-host disease (GVHD). METHODS: In mice, an allogeneic GVHD model was established by transferring bone marrow (BM) and purified spl ... Full text Link to item Cite

Microglia Preserve Visual Function in a Mouse Model of Retinitis Pigmentosa with Rhodopsin-P23H Mutant.

Journal Article Adv Exp Med Biol · 2023 Most forms of outer retinal degenerative diseases involve the ectopic accumulation of microglia/macrophages in the subretinal space, including retinitis pigmentosa. However, their role in the loss of photoreceptor function during retinal degeneration remai ... Full text Link to item Cite

Microglia Drive Pockets of Neuroinflammation in Middle Age.

Journal Article J Neurosci · May 11, 2022 During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and ot ... Full text Link to item Cite

Allergy and Immune-Mediated Tissue Injury

Chapter · January 1, 2022 The immune system serves a protective role in our defense against pathogens. However, the immune response may sometimes be misdirected or exaggerated in a way that results in pathology. Such inappropriate responses are termed as "hypersensitivity reactions ... Full text Cite

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.

Journal Article Transplant Cell Ther · October 2021 Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Pro ... Full text Link to item Cite

Meibomian gland dysfunction is suppressed via selective inhibition of immune responses by topical LFA-1/ICAM antagonism with lifitegrast in the allergic eye disease (AED) model.

Journal Article Ocul Surf · July 2021 PURPOSE: The etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meib ... Full text Link to item Cite

Mucosal-associated invariant T cell responses differ by sex in COVID-19.

Journal Article Med · June 11, 2021 BACKGROUND: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood. METHODS: We carried out sex-balanced sampling of peripheral blood mon ... Full text Open Access Link to item Cite

BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.

Journal Article Blood · May 6, 2021 Patients with chronic graft-versus-host disease (cGVHD) have increased B cell-activating factor (BAFF) levels, but whether BAFF promotes disease after allogeneic bone marrow transplantation (allo-BMT) remains unknown. In a major histocompatibility complex- ... Full text Link to item Cite

In vivo quantitative analysis of anterior chamber white blood cell mixture composition using spectroscopic optical coherence tomography.

Journal Article Biomed Opt Express · April 1, 2021 Anterior uveitis is the most common form of intraocular inflammation, and one of its main signs is the presence of white blood cells (WBCs) in the anterior chamber (AC). Clinically, the true composition of cells can currently only be obtained using AC para ... Full text Link to item Cite

The cornea IV immunology, infection, neovascularization, and surgery chapter 1: Corneal immunology.

Journal Article Exp Eye Res · April 2021 PURPOSE: of Review: This review offers an informed and up-to-date insight on the immune profile of the cornea and the factors that govern the regulation of such a unique immune environment. SUMMARY: The cornea is a unique tissue that performs the specializ ... Full text Link to item Cite

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

Journal Article Nat Commun · February 17, 2021 SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral bloo ... Full text Open Access Link to item Cite

Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy.

Journal Article Int J Mol Sci · October 12, 2020 Conjunctiva-associated tissue (CALT) is assumed to play a crucial role in the immune system of the ocular surface. Its function in several ocular surface diseases (OSD) is still not fully understood. This study investigates the function of CALT in mouse mo ... Full text Link to item Cite

Microglia versus Monocytes: Distinct Roles in Degenerative Diseases of the Retina.

Journal Article Trends Neurosci · June 2020 Unlike in the healthy mammalian retina, macrophages in retinal degenerative states are not solely comprised of microglia but may include monocyte-derived recruits. Recent studies have applied transgenics, lineage-tracing, and transcriptomics to help deciph ... Full text Link to item Cite

The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options.

Journal Article J Ocul Pharmacol Ther · April 2020 Homeostasis of the lacrimal functional unit is needed to ensure a well-regulated ocular immune response comprising innate and adaptive phases. When the ocular immune system is excessively stimulated and/or immunoregulatory mechanisms are disrupted, the bal ... Full text Link to item Cite

scDAPA: detection and visualization of dynamic alternative polyadenylation from single cell RNA-seq data.

Journal Article Bioinformatics · February 15, 2020 Featured Publication MOTIVATION: Alternative polyadenylation (APA) plays a key post-transcriptional regulatory role in mRNA stability and functions in eukaryotes. Single cell RNA-seq (scRNA-seq) is a powerful tool to discover cellular heterogeneity at gene expression level. Gi ... Full text Link to item Cite

Neutrophil L-Plastin Controls Ocular Paucibacteriality and Susceptibility to Keratitis.

Journal Article Front Immunol · 2020 Why ocular mucosa is paucibacterial is unknown. Many different mechanisms have been suggested but the comprehensive experimental studies are sparse. We found that a deficiency in L-plastin (LCP1), an actin bundling protein, resulted in an ocular commensal ... Full text Link to item Cite

Large-scale death of retinal astrocytes during normal development is non-apoptotic and implemented by microglia.

Journal Article PLoS Biol · October 2019 Featured Publication Naturally occurring cell death is a fundamental developmental mechanism for regulating cell numbers and sculpting developing organs. This is particularly true in the nervous system, where large numbers of neurons and oligodendrocytes are eliminated via apo ... Full text Link to item Cite

Complement and CD4+ T cells drive context-specific corneal sensory neuropathy.

Journal Article Elife · August 15, 2019 Featured Publication Whether complement dysregulation directly contributes to the pathogenesis of peripheral nervous system diseases, including sensory neuropathies, is unclear. We addressed this important question in a mouse model of ocular HSV-1 infection, where sensory nerv ... Full text Link to item Cite

Elucidatiing niche-associated function of retinal microglia at the single cell level

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

PRCD is essential for high-fidelity photoreceptor disc formation.

Journal Article Proc Natl Acad Sci U S A · June 25, 2019 Featured Publication Progressive rod-cone degeneration (PRCD) is a small protein residing in the light-sensitive disc membranes of the photoreceptor outer segment. Until now, the function of PRCD has remained enigmatic despite multiple demonstrations that its mutations cause b ... Full text Link to item Cite

Immune cells in the retina and choroid: Two different tissue environments that require different defenses and surveillance.

Journal Article Prog Retin Eye Res · May 2019 Featured Publication In the eye immune defenses must take place in a plethora of differing microenvironments ranging from the corneal and conjunctival epithelia facing the external environment to the pigmented connective tissue of the uveal tract containing smooth muscle, bloo ... Full text Link to item Cite

Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration.

Journal Article Immunity · March 19, 2019 Featured Publication Microglia from different nervous system regions are molecularly and anatomically distinct, but whether they also have different functions is unknown. We combined lineage tracing, single-cell transcriptomics, and electrophysiology of the mouse retina and sh ... Full text Link to item Cite

Resolvin D1 treatment on goblet cell mucin and immune responses in the chronic allergic eye disease (AED) model.

Journal Article Mucosal Immunol · January 2019 Featured Publication Severe, chronic eye allergy is an understudied, vision-threatening condition. Treatments remain limited. We used a mouse model of severe allergic eye disease (AED) to determine whether topical application of the pro-resolution mediator Resolvin D1 (RvD1) t ... Full text Link to item Cite

Fate Mapping In Vivo to Distinguish Bona Fide Microglia Versus Recruited Monocyte-Derived Macrophages in Retinal Disease.

Journal Article Methods Mol Biol · 2019 Featured Publication With the new understanding that adult microglia in mice have embryonic origins and are maintained in situ throughout life, it has become pertinent to now understand how these unique cells differ from monocyte-derived macrophages. The latter are recruited i ... Full text Link to item Cite

Identification of a Unique Subretinal Microglia Type in Retinal Degeneration Using Single Cell RNA-Seq.

Journal Article Adv Exp Med Biol · 2019 As the resident macrophages of central nervous system, microglia reside in the plexiform and nerve fiber layers of the retina. In degenerative diseases, monocyte-derived macrophages can be recruited to the retina, and histopathology shows abnormal accumula ... Full text Link to item Cite

SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.

Journal Article JCI Insight · October 4, 2018 Featured Publication Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HCT). The tyrosine kinase SYK contributes to both acute and chronic GVHD development, making it an attractive target for GVHD prevention. Entospletinib (EN ... Full text Link to item Cite

New concepts in macrophage ontogeny in the adult neural retina.

Journal Article Cell Immunol · August 2018 Featured Publication The number of neurons dedicated to vision itself is thought to be greater than the sum of the four other senses combined. Yet, little attention has been payed to the retina as compared to elsewhere in the central nervous system with respect to microglia, t ... Full text Link to item Cite

Neutrophils cause obstruction of eyelid sebaceous glands in inflammatory eye disease in mice.

Journal Article Sci Transl Med · July 25, 2018 Featured Publication Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the o ... Full text Link to item Cite

Tear leukocyte phenotyping in meibomian gland dysfunction by large parameter flow cytometry

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

Gene Therapy for Modulation of T-Cell-Mediated Immune Response Provoked by Corneal Transplantation.

Journal Article Hum Gene Ther · April 2018 Corneal transplantation (keratoplasty) is the most common type of tissue replacement in the world. The increased rate of graft rejection after keratoplasty is a central problem for repeated transplantations and in inflamed host corneas. It has been shown t ... Full text Link to item Cite

Effect of Anti-C5a Therapy in a Murine Model of Early/Intermediate Dry Age-Related Macular Degeneration.

Journal Article Invest Ophthalmol Vis Sci · February 1, 2018 PURPOSE: A large body of evidence supports a central role for complement activation in the pathobiology of age-related macular degeneration (AMD), including plasma complement component 5a (C5a). Interestingly, C5a is a chemotactic agent for monocytes, a ce ... Full text Link to item Cite

Induction and Characterization of the Allergic Eye Disease Mouse Model.

Journal Article Methods Mol Biol · 2018 Ocular IgE-associated allergy ranges from mild disease (seasonal and perennial allergic conjunctivitis) to more chronic/severe and vision-threatening forms (atopic and vernal keratoconjunctivitis). Whereas mild forms of disease have been studied extensivel ... Full text Link to item Cite

Interleukin-6 neutralization prolongs corneal allograft survival.

Journal Article Curr Trends Immunol · 2018 The purpose of this study is to determine the effect of systemic blockade of Interleukin-6 (IL-6) on allosensitization, regulatory T cell frequencies and suppressive phenotype, and allograft survival rates in a mouse model of corneal transplantation. Allog ... Link to item Cite

The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor.

Journal Article EBioMedicine · August 2017 Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Severa ... Full text Link to item Cite

A Commencement for Eye Commensals.

Journal Article Immunity · July 18, 2017 Featured Publication "Paucibacterial" levels of the normal eye surface have left immunologists wondering whether a true microbiome exists there. In this issue of Immunity, St. Leger et al. (2017) address this head-on, discovering a naturally existing commensal in mice that ind ... Full text Link to item Cite

New insights into mononuclear phagocyte biology from the visual system.

Journal Article Nat Rev Immunol · May 2017 Featured Publication Major advances in mononuclear phagocyte biology have been made but key questions pertinent to their roles in health and disease remain, including in the visual system. One problem concerns how dendritic cells can trigger immune responses from certain tight ... Full text Link to item Cite

Recipient-Derived BAFF and Alloantigen Synergistically Activate B Cells in Murine Chronic Gvhd

Conference Blood · December 2, 2016 Featured Publication AbstractIncreased B cell-activating factor (BAFF) and aberrant B cell survival and activation are associated with chronic graft versus host disease (cGVHD) in patients. Whether excessive BAFF production has ... Full text Cite

CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.

Journal Article J Mol Med (Berl) · November 2016 UNLABELLED: In this study, the role of CX3CR1 in the progression of diabetic retinopathy (DR) was investigated. The retinas of wild-type (WT), CX3CR1 null (CX3CR1gfp/gfp, KO), and heterozygous (CX3CR1+/gfp, Het) mice were compared in the presence and absen ... Full text Link to item Cite

Method for single illumination source combined optical coherence tomography and fluorescence imaging of fluorescently labeled ocular structures in transgenic mice.

Journal Article Exp Eye Res · October 2016 In vivo imaging permits longitudinal study of ocular disease processes in the same animal over time. Two different in vivo optical imaging modalities - optical coherence tomography (OCT) and fluorescence - provide important structural and cellular data res ... Full text Link to item Cite

Microglia and monocyte-derived macrophage responses to light damage differ across mouse strains

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy.

Journal Article JCI Insight · August 4, 2016 Featured Publication Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell ... Full text Link to item Cite

Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring.

Journal Article JCI Insight · August 4, 2016 Featured Publication Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase family 1 (ALDH1) is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibro ... Full text Link to item Cite

Secondary allergic T cell responses are regulated by dendritic cell-derived thrombospondin-1 in the setting of allergic eye disease.

Journal Article J Leukoc Biol · August 2016 Featured Publication Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, o ... Full text Link to item Cite

Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina.

Journal Article Sci Rep · February 9, 2016 Featured Publication The recent paradigm shift that microglia are yolk sac-derived, not hematopoietic-derived, is reshaping our knowledge about the isolated role of microglia in CNS diseases, including degenerative conditions of the retina. However, unraveling microglial-speci ... Full text Link to item Cite

Partial denervation of sub-basal axons persists following debridement wounds to the mouse cornea.

Journal Article Lab Invest · November 2015 Although sensory reinnervation occurs after injury in the peripheral nervous system, poor reinnervation in the elderly and those with diabetes often leads to pathology. Here we quantify sub-basal axon density in the central and peripheral mouse cornea over ... Full text Link to item Cite

Linking immune responses with fibrosis in allergic eye disease.

Journal Article Curr Opin Allergy Clin Immunol · October 2015 PURPOSE OF REVIEW: Here, we explore an emerging theme in the literature, which is the role of dendritic cells in the causation of fibrosis. To fully appreciate this pathway to disease, we also review the most recent literature regarding dendritic cell biol ... Full text Link to item Cite

Immune Responses at the Ocular Surface

Journal Article Acta Ophthalmologica · October 2015 SummaryImmune‐mediated diseases of the ocular surface are relatively broad in their respective etiologies, which can involve infection, autoimmunity, or allergy. Despite this range, immune responses often converge upstream ... Full text Cite

Regulation of age-related macular degeneration-like pathology by complement factor H.

Journal Article Proc Natl Acad Sci U S A · June 9, 2015 Featured Publication Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged ... Full text Link to item Cite

Involvement of corneal lymphangiogenesis in a mouse model of allergic eye disease.

Journal Article Invest Ophthalmol Vis Sci · May 2015 Featured Publication PURPOSE: The contribution of lymphangiogenesis (LA) to allergy has received considerable attention and therapeutic inhibition of this process via targeting VEGF has been considered. Likewise, certain inflammatory settings affecting the ocular mucosa can tr ... Full text Link to item Cite

CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease.

Journal Article Invest Ophthalmol Vis Sci · August 19, 2014 Featured Publication PURPOSE: We characterized antigen-presenting cell (APC)-relevant chemokine receptor expression in dry eye disease (DED), and investigated the effect of topical CC chemokine receptor (CCR)-7 blockade specifically on Th17 cell immunity and dry eye disease se ... Full text Link to item Cite

Cytokine deposition alters leukocyte morphology and initial recruitment of monocytes and γδT cells after corneal injury.

Journal Article Invest Ophthalmol Vis Sci · April 28, 2014 PURPOSE: An in vivo mouse model reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously 2 weeks after a single 1.5-mm corneal debridement wound made with a dulled blade. When 1.5-mm wounds are made by a rotating burr so that the ... Full text Link to item Cite

Single Source Fluorescence Imaging/Blue Optical Coherence Tomography in a GFP Mouse Model

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

CCR7 is critical in the induction and maintenance of Th17 immunity in dry eye disease

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Novel Mouse Model of Severe Ocular Allergy Reveals a Key Role for Pathogenic Th17 Cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

CCL-21 conditioned regulatory T cells induce allotolerance through enhanced homing to lymphoid tissue.

Journal Article J Immunol · January 15, 2014 Regulatory T cells (Tregs) are instrumental in the induction and maintenance of tolerance, including in transplantation. Tregs induce allotolerance by interacting with APCs and T cells, interactions that require their proper homing to the lymphoid tissues. ... Full text Link to item Cite

Pathobiology of Immune-Mediated Diseases of the Ocular Surface

Chapter · January 1, 2014 Ocular surface disease describes a spectrum of disorders that affect the normal structure and function of the conjunctiva, cornea, and supportive glandular network. A significant proportion of such diseases have an immune etiology, such as in allergic and ... Full text Cite

Chronic dry eye disease is principally mediated by effector memory Th17 cells.

Journal Article Mucosal Immunol · January 2014 Recent experimental and clinical data suggest that there is a link between dry eye disease (DED) and T-cell-mediated immunity. However, whether these immune responses are a consequence or cause of ocular surface inflammation remains to be determined. Thus ... Full text Link to item Cite

CNS inflammation and bone marrow neuropathy in type 1 diabetes.

Journal Article Am J Pathol · November 2013 By using pseudorabies virus expressing green fluorescence protein, we found that efferent bone marrow-neural connections trace to sympathetic centers of the central nervous system in normal mice. However, this was markedly reduced in type 1 diabetes, sugge ... Full text Link to item Cite

Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis.

Journal Article Invest Ophthalmol Vis Sci · April 3, 2013 PURPOSE: A majority of experimental data on dry eye disease (DED) immunopathogenesis have been derived from a murine model of DED that combines desiccating environmental stress with systemic muscarinic acetylcholine receptor (mAChR) inhibition. However, to ... Full text Link to item Cite

New twists to an old story: novel concepts in the pathogenesis of allergic eye disease.

Journal Article Curr Eye Res · March 2013 The prevalence of allergy is rising globally at a very significant rate, which is currently at 20-40% of individuals in westernized nations. In the eye, allergic conditions can take on the acute form such as in seasonal and perennial allergic conjunctiviti ... Full text Link to item Cite

Ocular mucosal CD11b+ and CD103+ mouse dendritic cells under normal conditions and in allergic immune responses.

Journal Article PLoS One · 2013 Steady state dendritic cells (DC) found in non-lymphoid tissue sites under normal physiologic conditions play a pivotal role in triggering T cell responses upon immune provocation. CD11b+ and CD103+ DC have received considerable attention in this regard. H ... Full text Link to item Cite

Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

Journal Article PLoS One · 2013 A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such mo ... Full text Link to item Cite

Gamma-irradiation reduces the allogenicity of donor corneas.

Journal Article Invest Ophthalmol Vis Sci · October 1, 2012 PURPOSE: To evaluate the utility and allogenicity of gamma-irradiated corneal allografts. METHODS: Corneal buttons were harvested from C57BL/6 mice and decellularized with gamma irradiation. Cell viability was assessed using TUNEL and viability/cytotoxicit ... Full text Link to item Cite

Blocking CCR7 at the ocular surface impairs the pathogenic contribution of dendritic cells in allergic conjunctivitis.

Journal Article Am J Pathol · June 2012 CCR7 plays a key role in mobilizing tissue dendritic cells (DCs) to the lymphoid compartment for consequent elicitation of adaptive immunity. Interfering with CCR7 function therapeutically would therefore be anticipated to inhibit the progression of atopic ... Full text Link to item Cite

Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation.

Journal Article J Leukoc Biol · April 2012 Significant interest has been focused on the use of ex vivo-manipulated DCs to optimally induce transplant tolerance and promote allograft survival. Although it is understood that donor-derived, tolerogenic DCs suppress the direct pathway of allosensitizat ... Full text Link to item Cite

Dependence of corneal stem/progenitor cells on ocular surface innervation.

Journal Article Invest Ophthalmol Vis Sci · February 21, 2012 PURPOSE: Neurotrophic keratopathy (NK) is a corneal degeneration associated with corneal nerve dysfunction. It can cause corneal epithelial defects, stromal thinning, and perforation. However, it is not clear if and to which extent epithelial stem cells ar ... Full text Link to item Cite

Corneal penetration of topical and subconjunctival bevacizumab.

Journal Article Invest Ophthalmol Vis Sci · November 7, 2011 PURPOSE: To investigate the ability of bevacizumab to penetrate the cornea after topical application or subconjunctival injection. METHODS: Bevacizumab 1% was topically applied three times a day to the corneas of mice (BALB/c) with intact corneas (n = 14), ... Full text Link to item Cite

Characterization of Langerin-expressing dendritic cell subsets in the normal cornea.

Journal Article Invest Ophthalmol Vis Sci · June 28, 2011 PURPOSE: In addition to Langerhans cells (LCs), other dendritic cells (CD11c(+)) have recently been shown to express Langerin (c-type lectin). In skin, (non-LC) Langerin+ dendritic cells initiate adaptive immunity. However, whether such dendritic cells (DC ... Full text Link to item Cite

Interferon-γ-secreting NK cells promote induction of dry eye disease.

Journal Article J Leukoc Biol · June 2011 NK cells have been increasingly reported to be an important effector in autoimmune diseases. However, nothing is known in this regard in DED, the most common eye pathology, which is characterized by sustained inflammation on the ocular surface. In the pres ... Full text Link to item Cite

Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.

Journal Article J Exp Med · May 9, 2011 Lymphangiogenesis plays an important role in tumor metastasis and transplant outcome. Here, we show that thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein and naturally occurring inhibitor of angiogenesis inhibits lymphangiogenesis i ... Full text Link to item Cite

Effect of topical azithromycin on corneal innate immune responses.

Journal Article Invest Ophthalmol Vis Sci · April 19, 2011 PURPOSE: To determine the effect of azithromycin (AZM) in a murine model of corneal inflammation. METHODS: The effect of topical AZM was studied in murine corneal inflammation. Corneal inflammation was induced by thermal cautery in BALB/c mice. Leukocyte i ... Full text Link to item Cite

Suppression of inflammatory corneal lymphangiogenesis by application of topical corticosteroids.

Journal Article Arch Ophthalmol · April 2011 OBJECTIVES: To analyze whether topical application of corticosteroids inhibits inflammatory corneal lymphangiogenesis and to study the potential underlying antilymphangiogenic mechanisms. METHODS: Inflammatory corneal neovascularization was induced by sutu ... Full text Link to item Cite

Retinal pigment epithelial cells induce foxp3(+) regulatory T cells via membrane-bound TGF-β.

Journal Article Ocul Immunol Inflamm · December 2010 PURPOSE: It is speculated that retinal pigment epithelial (RPE) cells convert naïve T cells into regulatory T cells (Tregs) via soluble factors such as transforming growth factor beta (TGF-β). Yet presence or absence of similar membrane-bound mechanisms on ... Full text Link to item Cite

Corneal graft rejection

Chapter · December 1, 2010 Full text Cite

Thrombospondin-1 derived from APCs regulates their capacity for allosensitization.

Journal Article J Immunol · October 15, 2010 Thrombospondin (TSP)-1 is a matricellular glycoprotein with immunoregulatory properties, which include inhibition of APC function. We show in transplantation that TSP-1 inhibits T cell allosensitization and consequently suppresses immune rejection. This wa ... Full text Link to item Cite

Effects of topical and subconjunctival bevacizumab in high-risk corneal transplant survival.

Journal Article Invest Ophthalmol Vis Sci · May 2010 PURPOSE: To investigate whether corneal graft survival could be improved by topical or subconjunctival bevacizumab in a murine model of vascularized high-risk corneal transplantation. METHODS: Before corneal transplantation, intrastromal sutures were place ... Full text Link to item Cite

Identification and Function of Novel Langerin Positive Dendritic Cells in the Cornea

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2010 Link to item Cite

Regulatory Effects of Early NK Cell Responses on Adaptive Immunity in Dry Eye Disease

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2010 Link to item Cite

Th17/IL17 Mediates Autoimmunity-Dependent Corneal Lymphangiogenesis in Dry Eye Disease

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2010 Link to item Cite

Corneal graft rejection

Chapter · March 3, 2010 Full text Cite

Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation.

Journal Article Invest Ophthalmol Vis Sci · February 2010 PURPOSE: Chemokine receptor 7 (CCR7) is a key homing molecule for immune cell trafficking, including corneal antigen-presenting cell (APC) migration from the inflamed cornea to draining lymph nodes (LNs). Here, the authors investigated the effect of CCR7-f ... Full text Link to item Cite

Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators.

Journal Article Invest Ophthalmol Vis Sci · October 2009 PURPOSE: Resolvins and lipoxins are lipid mediators generated from essential polyunsaturated fatty acids that are the first dual anti-inflammatory and pro-resolving signals identified in the resolution phase of inflammation. Here the authors investigated t ... Full text Link to item Cite

Characterization of effector T cells in dry eye disease.

Journal Article Invest Ophthalmol Vis Sci · August 2009 PURPOSE: Dry eye disease (DED) is associated with ocular surface inflammation that is thought to be mediated primarily by CD4 T cells. The purpose of this study was to investigate whether this T cell-mediated immune response is generated in the lymphoid co ... Full text Link to item Cite

Depletion of passenger leukocytes from corneal grafts: an effective means of promoting transplant survival?

Journal Article Invest Ophthalmol Vis Sci · July 2009 PURPOSE: To develop and compare effective strategies for depleting graft-derived passenger leukocytes that include antigen-presenting cells from corneal buttons and to assess the effectiveness of this strategy in promoting graft survival using a high-risk ... Full text Link to item Cite

Regulation of blood vessel versus lymphatic vessel growth in the cornea.

Journal Article Invest Ophthalmol Vis Sci · April 2009 PURPOSE: In the present study, the authors developed novel models to stimulate blood vessel formation (hemangiogenesis) versus lymphatic vessel formation (lymphangiogenesis) in the cornea. METHODS: Micropellets loaded with high-dose (80 ng) or low-dose (12 ... Full text Link to item Cite

'Chimeric' grafts assembled from multiple allodisparate donors enjoy enhanced transplant survival.

Journal Article Am J Transplant · March 2009 Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graf ... Full text Link to item Cite

Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression.

Journal Article J Immunol · February 1, 2009 Dry eye disease (DED), an inflammatory autoimmune disorder affecting the ocular surface, degrades visual performance and the quality of life of >10 million people in the United States alone. The primary limitation in the effective treatment of DED is an in ... Full text Link to item Cite

Levels of Foxp3 in regulatory T cells reflect their functional status in transplantation.

Journal Article J Immunol · January 1, 2009 Foxp3 expressing CD4(+)CD25(+) regulatory T cells (Tregs) have been shown to prevent allograft rejection in clinical and animal models of transplantation. However, the role of Foxp3 in regulating Treg function, and the kinetics and mechanism of action of T ... Full text Link to item Cite

Characterization of intraocular immunopathology following intracameral inoculation with alloantigen.

Journal Article Mol Vis · March 26, 2008 PURPOSE: Anterior chamber-associated immune deviation (ACAID) is a form of peripheral tolerance achieved via intracameral antigen inoculation. It is well known that ACAID effectively down-regulates potentially destructive immunities such as delayed-type hy ... Link to item Cite

The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens.

Journal Article Mol Vis · 2008 PURPOSE: Anterior chamber associated immune deviation (ACAID) is an antigen-specific form of peripheral immune tolerance that is induced to exogenous antigens placed in the ocular anterior chamber, which leads to a suppression in delayed-type hypersensitiv ... Link to item Cite

Autoimmune dacryoadenitis of NOD/LtJ mice and its subsequent effects on tear protein composition.

Journal Article Am J Pathol · October 2007 Sjögren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands. Although, we previously established a good correlation between SjS ... Full text Link to item Cite

IL-4-STAT6 signal transduction-dependent induction of the clinical phase of Sjögren's syndrome-like disease of the nonobese diabetic mouse.

Journal Article J Immunol · July 1, 2007 NOD.B10-H2(b) and NOD/LtJ mice manifest, respectively, many features of primary and secondary Sjögren's syndrome (SjS), an autoimmune disease affecting primarily the salivary and lacrimal glands leading to xerostomia (dry mouth) and xerophthalmia (dry eyes ... Full text Link to item Cite

Preventing stem cell incorporation into choroidal neovascularization by targeting homing and attachment factors.

Journal Article Invest Ophthalmol Vis Sci · January 2005 PURPOSE: The primary cause of vision loss in people more than 50 years of age in developed nations is age-related macular degeneration (ARMD). The wet form of ARMD is characterized by choroidal neovascularization (CNV). A prior study has shown that adult h ... Full text Link to item Cite

Optimization of lentiviral gene delivery to the retinal pigment epithelium in vivo

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · May 1, 2003 Link to item Cite

Viral vectors for efficient gene delivery to RPE cells.

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · March 15, 2001 Link to item Cite