A5007857364- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Glaucoma and retinal disorders
- Connexins and lens biology
- Retinoids in leukemia and cellular processes
- Photoreceptor and optogenetics research
- Retinal and Macular Surgery
- Ocular Diseases and Behçet’s Syndrome
- Retinal and Optic Conditions
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Retinal Imaging and Analysis
- Barrier Structure and Function Studies
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Neurological Disease Mechanisms and Treatments
- Cell Adhesion Molecules Research
- Intraocular Surgery and Lenses
- Corneal Surgery and Treatments
- Receptor Mechanisms and Signaling
- bioluminescence and chemiluminescence research
- Systemic Lupus Erythematosus Research
- Retinopathy of Prematurity Studies
- Ubiquitin and proteasome pathways
National Eye Institute
2014-2024
National Institutes of Health
2013-2024
NTL Institute for Applied Behavioral Science
2019
Core Laboratories (United States)
2008
University of California, Santa Barbara
1986-2005
BIC (France)
2004-2005
Office of Extramural Research
2003
Johns Hopkins University
2003
University of Washington
1997-2000
Baylor College of Medicine
1998
Microglia, the primary resident immune cells of central nervous system (CNS), exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions surveillance tissue repair. Although age-related changes in microglial activation have been implicated pathogenesis neurodegenerative diseases aging, how microglia influenced by aging not fully understood. In this study, we employed live imaging retinal situ compare morphology behavioral...
Research Article2 July 2015Open Access Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration Lian Zhao Unit on Neuron-Glia Interactions in Retinal Disease, National Eye institute, Institutes Health, Bethesda, MD, USA Search for more papers by this author Matthew K Zabel Xu Wang Wenxin Ma Parth Shah Robert N Fariss Biological Imaging Core, Haohua Qian Visual Function Christopher Parkhurst Department Neuroscience and Physiology, Skirball Institute, New...
Purpose Microglia represent the primary resident immune cells in CNS, and have been implicated pathology of neurodegenerative diseases. Under basal or "resting" conditions, microglia possess ramified morphologies exhibit dynamic surveying movements their processes. Despite prominence this phenomenon, function regulation microglial morphology behavior are incompletely understood. We investigate here whether how neurotransmission regulates behavior. Methods employed an ex vivo mouse retinal...
VEGF-B, a homolog of VEGF discovered long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it received little attention from the field. In this study, using different animal models and multiple types vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, critical their survival. Importantly, survival effect only on endothelial but also pericytes, smooth muscle stem/progenitor cells. vivo, targeting inhibited both...
Chronic retinal inflammation in the form of activated microglia and macrophages are implicated etiology neurodegenerative diseases retina, including age-related macular degeneration, diabetic retinopathy, glaucoma. However, molecular biomarkers targeted therapies for immune cell activation these disorders currently lacking. To address this, we investigated involvement role translocator protein (TSPO), a biomarker microglial astrocyte gliosis brain context inflammation. Here, find that TSPO...
Microglia, the principal resident immune cell of CNS, exert significant influence on neurons during development and in pathological situations. However, if how microglia contribute to normal neuronal function mature uninjured CNS is not well understood. We used model adult mouse retina, a part amenable structural functional analysis, investigate constitutive role by depleting from retina sustained manner using genetic methods. discovered that are acutely required for maintenance retinal...
Five members of a novel Ca(2+)-binding protein subfamily (CaBP), with 46-58% sequence similarity to calmodulin (CaM), were identified in the vertebrate retina. Important differences between these proteins and CaM include alterations within their second EF-hand loop that render motifs inactive Ca(2+) coordination fact central alpha-helixes are extended by one alpha-helical turn. CaBP1 CaBP2 contain consensus for N-terminal myristoylation, similar recoverin fatty acid acylated vitro. The...
Microglia and Müller cells are prominent participants in retinal responses to injury disease that shape eventual tissue adaptation or damage. This investigation examined how microglia interact with each other following initial microglial activation.Mouse were cultured alone, co-cultured activated unactivated microglia, their morphological, molecular, functional evaluated. cell-feedback signaling was studied using cell-conditioned media. Corroborative vivo analyses of microglia-Müller cell...
Background Age-related macular degeneration (AMD) is a leading cause of legal blindness in the elderly industrialized word. While immune system retina likely to be important AMD pathogenesis, cell biology underlying disease incompletely understood. Clinical and basic science studies have implicated alterations retinal pigment epithelium (RPE) layer as locus early change. Also, microglia, resident cells retina, been observed translocate from their normal position inner accumulate subretinal...
purpose. Retinal microglia have been implicated in the pathogenesis of various retinal diseases, but their basic function and cellular phenotype remain incompletely understood. Here, authors used a novel ex vivo imaging preparation to examine behavioral living intact tissue response injury. methods. Fluorescence-labeled explants from CX3CR1+/GFP transgenic mice were observed using time-lapse confocal imaging. High spatial temporal resolution parameters follow dynamic microglial behavior real...
Microglia in the central nervous system display a marked structural dynamism their processes resting state. This dynamic behavior, which may play constitutive surveying role uninjured neural parenchyma, is also highly responsive to tissue injury. The of CX3CR1, chemokine receptor expressed microglia, regulating microglia morphology and behavior state after laser-induced focal injury was examined.Time-lapse confocal imaging retinal explants used evaluate labeled with green fluorescent protein...
Morphogenesis of photoreceptor outer segment disks appears to occur by an evagination the ciliary plasma membrane (Steinberg et al., J Comp Neurol 190:501-519, '80). We tested if polymerized actin (F-actin) was necessary for regulation this postulated process incubating Xenopus eyecups with 5 or 25 microM cytochalasin D 6-28 hours. During second hour, incubation medium contained 3H-leucine. Both concentrations resulted in: 1) dissolution rhodamine-phalloidin labeling pattern photoreceptors,...
Retinitis pigmentosa (RP), a disease characterized by the progressive degeneration of mutation‐bearing photoreceptors, is significant cause incurable blindness in young worldwide. Recent studies have found that activated retinal microglia contribute to photoreceptor demise via phagocytosis and proinflammatory factor production, however mechanisms regulating these contributions are not well‐defined. In this study, we investigate role CX3CR1, microglia‐specific receptor, microglia‐mediated...
Chemokine signaling via CX3CL1-CX3CR1 helps regulate homeostasis in the population of microglia adult mouse retina.
Distinct mutations in the centrosomal-cilia protein CEP290 lead to diverse clinical findings syndromic ciliopathies. We show that localizes transition zone ciliated cells, precisely region of Y-linkers between central microtubules and plasma membrane. To create models CEP290-associated ciliopathy syndromes, we generated Cep290(ko/ko) Cep290(gt/gt) mice produce no or a truncated protein, respectively. exhibit early vision loss die from hydrocephalus. Retinal photoreceptors lack connecting...
Age-related macular degeneration (AMD), a leading contributor of vision loss, currently lacks comprehensive treatment. While AMD histopathology involves retinal pigment epithelium (RPE) injury associated with immune cell infiltration, the nature responses to RPE remains undefined. We induced pharmacologically and genetically in transgenic mouse models which microglia systemic monocytes were separately tagged, enabling spatial temporal dissection relative contributions vs. post-injury...
RGS9 is a member of the RGS family GTPase accelerating proteins (GAPs) for heterotrimeric G proteins. We have explored its contribution to acceleration in mammalian rod and cone photoreceptors. When was specifically removed from detergent extracts outer segments by immunodepletion, lost nearly all their GAP activity stimulatable inhibitory subunit cGMP phosphodiesterase. Immunolocalization using monoclonal antibodies confocal microscopy revealed that present cones at significantly higher...
We developed a genetic mouse model of open-angle glaucoma by expression mutated myocilin (Myoc) in transgenic (Tg) mice. The Tyr423His point mutation, corresponding to the severe glaucoma-causing Tyr437His mutation human MYOC gene, was introduced into bacterial artificial chromosome DNA encoding full-length Myoc gene and long flanking regions. Both wild-type (Wt) Tg animals expressed tissues irido-corneal angle sclera. Expression induced accumulation cell cytoplasm prevented its secretion...