Journal ArticleCancer Res · November 4, 2024
Radiotherapy (RT) is commonly used to try to eliminate any remaining tumor cells following surgical resection of glioma. However, tumor recurrence is prevalent, highlighting the unmet medical need to develop therapeutic strategies to enhance the efficacy o ...
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Journal ArticleOcul 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleNat 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleAdvances in experimental medicine and biology · January 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 ...
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Journal ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience · May 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 ...
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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 ...
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Journal ArticleTransplant 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 ...
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Journal ArticleOcul 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 ...
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Journal ArticleMed · 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 ...
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Journal ArticleBlood · 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- ...
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Journal ArticleBiomed 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 ...
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Journal ArticleExp 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 ...
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Journal ArticleNat 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 ...
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Journal ArticleInt 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 ...
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Journal ArticleTrends 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleBioinformatics · February 15, 2020
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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 ...
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Journal ArticleFront 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 ...
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Journal ArticlePLoS Biol · October 2019
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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 ...
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Journal ArticleElife · August 15, 2019
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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 ...
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Journal ArticleProc Natl Acad Sci U S A · June 25, 2019
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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 ...
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Journal ArticleProg Retin Eye Res · May 2019
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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 ...
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Journal ArticleImmunity · March 19, 2019
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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 ...
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Journal ArticleMucosal Immunol · January 2019
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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 ...
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Journal ArticleMethods Mol Biol · 2019
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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 ...
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Journal ArticleAdv 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 ...
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Journal ArticleJCI Insight · October 4, 2018
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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 ...
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Journal ArticleCell Immunol · August 2018
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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 ...
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Journal ArticleSci Transl Med · July 25, 2018
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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 ...
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Journal ArticleHum 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleMethods 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 ...
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Journal ArticleCurr 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 ...
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Journal ArticleEBioMedicine · 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 ...
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Journal ArticleImmunity · July 2017
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"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 ...
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Journal ArticleNat Rev Immunol · May 2017
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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 ...
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ConferenceBlood · December 2, 2016
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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 ...
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Journal ArticleJ 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 ...
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Journal ArticleExp 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 ...
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Journal ArticleJCI Insight · August 4, 2016
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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 ...
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Journal ArticleJCI Insight · August 4, 2016
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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 ...
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Journal ArticleJ Leukoc Biol · August 2016
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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 ...
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Journal ArticleSci Rep · February 9, 2016
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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 ...
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Journal ArticleLab 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 ...
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Journal ArticleCurr 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 ...
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Journal ArticleActa 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 ...
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Journal ArticleProc Natl Acad Sci U S A · June 9, 2015
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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 ...
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Journal ArticleInvest Ophthalmol Vis Sci · May 2015
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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 ...
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Journal ArticleInvest Ophthalmol Vis Sci · August 19, 2014
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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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleJ 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. ...
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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 ...
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Journal ArticleMucosal 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleCurr 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 ...
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Journal ArticlePLoS 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 ...
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Journal ArticlePLoS 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleInvest 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), ...
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Journal ArticleInvest 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleArch 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 ...
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Journal ArticleOcul 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleInvest 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleMol 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 ...
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Journal ArticleMol 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 ...
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Journal ArticleAm 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 ...
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Journal ArticleJ 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 ...
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Journal ArticleInvest 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 ...
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