A5021848689- Neuroinflammation and Neurodegeneration Mechanisms
- Ocular Surface and Contact Lens
- Immunotherapy and Immune Responses
- Corneal Surgery and Treatments
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Immune cells in cancer
- Neurological Disease Mechanisms and Treatments
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Mast cells and histamine
- Retinal Development and Disorders
- melanin and skin pigmentation
- Chemical Synthesis and Analysis
- Immune Cell Function and Interaction
- Biochemical and Molecular Research
- Allergic Rhinitis and Sensitization
- Cytomegalovirus and herpesvirus research
- Cancer-related gene regulation
- Retinal and Optic Conditions
- Neurogenesis and neuroplasticity mechanisms
- Amyotrophic Lateral Sclerosis Research
- Connexins and lens biology
- Flavonoids in Medical Research
- Ocular Infections and Treatments
Duke University
2016-2025
Durham Technical Community College
2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
2021
University of Madras
2020
Duke University Hospital
2019
Duke Medical Center
2014-2019
Massachusetts Eye and Ear Infirmary
2012-2018
Harvard University
1999-2018
Smith-Kettlewell Eye Research Institute
2008-2018
Rutgers, The State University of New Jersey
2015
Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells adoptive cell transfer, that transient elevation intraocular pressure (IOP) sufficient to induce T-cell infiltration into retina. This leads prolonged phase retinal ganglion degeneration persists after IOP returns normal level. Heat shock proteins (HSP)...
Abstract The recent paradigm shift that microglia are yolk sac-derived, not hematopoietic-derived, is reshaping our knowledge about the isolated role of in CNS diseases, including degenerative conditions retina. However, unraveling microglial-specific functions has been hindered by phenotypic overlap with monocyte-derived macrophages. latter differentiated from recruited monocytes neuroinflammation, Here we demonstrate use fate mapping wherein and cells endogenously labeled different...
Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked galectin-3 upregulation, sites mouse models human AMD. disease models, conditional deletion microglia led to phagocytosis defects...
SUMMARY Intraocular pressure is tightly regulated by the conventional outflow tissues, preventing ocular hypertension that leads to neurodegeneration of optic nerve, or glaucoma. Although macrophages reside throughout tract, their role in regulating intraocular remains unknown. Using macrophage lineage tracing approaches, we uncovered a dual ontogeny with distinct spatial organizations across mouse lifespan. Long-lived, resident tissue concentrated trabecular meshwork and Schlemm’s canal,...
During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells have profound impact on the function of nearby neurons. We others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, degree which properties vary during aging is largely unexplored. Here, we analyze manipulate within basal ganglia, circuits...
Significance The function of progressive rod-cone degeneration (PRCD) protein has remained a mystery since its gene and associated mutation were discovered as one the most common causes retinal in dogs. Furthermore, numerous mutations have been identified to cause human patients diagnosed with retinitis pigmentosa. Here, we generated PRCD knockout mouse found that functions at site photoreceptor disc morphogenesis where it is required keep newly forming discs flat they protrude from plasma...
Neutrophils obstruct the meibomian gland in a mouse model of inflammatory eye disease and correlate with severity patients dysfunction.
Steady state dendritic cells (DC) found in non-lymphoid tissue sites under normal physiologic conditions play a pivotal role triggering T cell responses upon immune provocation. CD11b+ and CD103+ DC have received considerable attention this regard. However, still unknown is whether such even exist the ocular mucosa, if so, what functions they shaping responses. We herein identified mucosa of wild-type (WT) Flt3-/- mice presence (i.e., CD11c+ MHCII+ CD103- F4/80+ Sirp-a+). (i.e. CD11b low...
Purpose.: The contribution of lymphangiogenesis (LA) to allergy has received considerable attention and therapeutic inhibition this process via targeting VEGF been considered. Likewise, certain inflammatory settings affecting the ocular mucosa can trigger pathogenic LA in naturally avascular cornea. Chronic inflammation allergic eye disease (AED) impacts conjunctiva cornea, leading sight threatening conditions. However, whether corneal is involved completely unknown. We addressed using a...
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 ocular HSV-1 infection, where nerve damage common clinical problem. Through genetic and pharmacologic targeting, we uncovered central role for C3 at morphological functional levels. Interestingly, CD4 T cells were facilitating complement-mediated damage. This same C3/CD4 cell axis...
Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads blindness in trachoma, pemphigoid, allergy. The indirect fibrogenic role of DCs via T cell activation inflammatory recruitment well documented. However, here we demonstrate that can directly induce fibrosis. mouse model allergic eye disease (AED), classical CD11b+ showed increased activity aldehyde dehydrogenase (ALDH), enzyme required for retinoic acid synthesis....
A new tetrafluorophenol activated resin that facilitates the use of 19F NMR to quantitate loading is presented. This provides a useful tool for acylation, and novel polymeric sulfonate ester generate sulfonamides. reacts with wide scope N-nucleophiles including primary secondary amines, anilines. methodology powerful pure single-compound library synthesis.
Abstract Inflammation in the eye is tightly regulated by multiple mechanisms that together contribute to ocular immune privilege. Many studies have shown it very difficult abrogate privileged mechanism called anterior chamber-associated deviation (ACAID). Previously, we showed retinal laser burn (RLB) one abrogated privilege (ACAID) bilaterally for an extended period of time. In effort explain inflammation nonburned eye, postulated neuronal signals initiated contralateral eye. this study,...
Severe, chronic eye allergy is an understudied, vision-threatening condition. Treatments remain limited. We used a mouse model of severe allergic disease (AED) to determine whether topical application the pro-resolution mediator Resolvin D1 (RvD1) terminates response. AED was induced by injection ovalbumin (OVA) followed challenge OVA daily. RvD1 applied topically prior OVA. Clinical symptoms were scored. Eye washes assayed for MUC5AC. After 7 days, eyes removed and number goblet cells, T...
Degenerative diseases of the outer retina, including age-related macular degeneration (AMD), are characterized by atrophy photoreceptors and retinal pigment epithelium (RPE). In these blinding diseases, macrophages known to accumulate ectopically at sites atrophy, but their ontogeny functional specialization within this atrophic niche remain poorly understood, especially in human context. Here, we uncovered a transcriptionally unique profile microglia, marked galectin-3 upregulation, mouse...
Summary It is known that inoculation of antigen into the anterior chamber (a.c.) a mouse eye induces a.c.-associated immune deviation (ACAID), which mediated in part by antigen-specific local and peripheral tolerance to inciting antigen. ACAID can also be induced vivo intravenous (i.v.) ex-vivo-generated tolerogenic antigen-presenting cells (TolAPC). The purpose this study was test if in-vitro-generated retinal antigen-pulsed TolAPC suppressed established experimental autoimmune uveitis...
Solid food processing wastes and by-products are cofermented with cheese whey to produce ethanol. The experimental procedure involves the use of an enzymatic process convert starch lactose into fermentable sugars. These reducing sugars then fermented alcohol by distiller's dried yeast a high-ethanol tolerant yeast, Saccharomyces cerevisiae. Cheese is used as wetting agent provides macro- micronutrients for microorganisms. Cofermenting whey, in presence high- low-temperature enzymes, induces...