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...

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...

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...

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.

Complement activation has been implicated as contributing to neurodegeneration in retinal and brain pathologies, but its role retinitis pigmentosa (RP), an inherited largely incurable photoreceptor degenerative disease, is unclear. We found that multiple complement components were markedly up-regulated retinas with human RP the rd10 mouse model, coinciding spatiotemporally degeneration, increased C3 expression localizing activated microglia. Genetic ablation of accelerated structural...

Constitutive TGFβ signaling is important in maintaining retinal neurons and blood vessels a factor contributing to the risk for age-related macular degeneration (AMD), disease involving neurodegeneration microglial activation. How microglia influences pathological neuroinflammation unclear. We discovered that ablation of receptor, TGFBR2, adult mice induced abnormal numbers, distribution, morphology, activation status, promoted gene expression profile. TGFBR2-deficient secondary gliotic...

The exudative, or the wet form of age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). A subretinal Matrigel (BD Biosciences, Bedford MA) model CNV described here, along with effects vascular endothelial growth factor (VEGF) neutralization on development and associated inflammation fibrosis.CNV was induced in adult Sprague-Dawley rats injection Matrigel. leukocyte infiltration collagen deposition were examined. VEGF Trap (Regeneron Pharmaceuticals,...

Age-related macular degeneration (AMD) has been associated with both accumulation of lipid and oxidative products, as well increased neuroinflammatory changes microglial activation in the outer retina. However, relationships between these factors are incompletely understood. 7-Ketocholesterol (7KCh) is a cholesterol oxidation product localized to retina prominent pro-inflammatory effects. To explore potential relationship 7KCh activation, we microglia aged mice investigated effects on...

Abstract We used the fluorescence in situ hybridization (FISH) method to show that chromosome 7 trisomy is associated with progression of human prostate cancer. Thirty‐six specimens including 15 primary carcinomas, 16 metastatic lesions, and 5 normal tissues, as well 2 carcinoma cell lines different tumorigenic potential, were examined for aneuplaidy. Our results showed androgen‐unresponsive line PC‐3 exhibited a significantly higher ratio total number than androgen‐responsive nontumorigenic...

Ciliary neurotrophic factor (CNTF) promotes photoreceptor survival but also suppresses electroretinogram (ERG) responses. This has caused concerns about whether CNTF is detrimental to the function of photoreceptors because it considered be a potential treatment for retinal degenerative disorders. Here we report that suppression ERG responses attributable negative regulation phototransduction machinery in rod photoreceptors. Intravitreal injection recombinant human protein rat results series...

Photoreceptor degeneration is a cause of irreversible vision loss in incurable blinding retinal diseases including retinitis pigmentosa (RP) and atrophic age-related macular degeneration. We found two separate mouse models photoreceptor that tamoxifen, selective estrogen receptor modulator drug previously linked with toxicity, paradoxically provided potent neuroprotective effects. In light-induced model, tamoxifen prevented onset apoptosis atrophy maintained near-normal levels...

The choroid, which provides vascular supply to the outer retina, demonstrates progressive degeneration in aging and age-related macular (AMD). However mechanisms that maintain or compromise choroidal homeostasis are obscure. We discovered ablation of macrophages via CSF1R blockade was associated with atrophy retinal pigment epithelial (RPE) changes including structural disruption, downregulation visual cycle genes, altered angiogenic factor expression. Suspending following enabled...

To explore the regulatory effects of sodium fluoride (NaF) exposure on apoptosis, oxidative stress, and matrix degradation in condylar chondrocytes subchondral osteoblasts using vitro vivo experiments. Condylar were treated with 5 mg/L 50 NaF, respectively, cell viability was detected. Chondrocyte apoptosis detected by flow cytometry western blotting. Oxidative inflammatory factor secretion, specific kits. RT-qPCR used to detect expression osteoblast phenotype genes. A rat model fluorosis...

As the global population ages, mechanisms underlying age-related susceptibility to delirium have attracted attention. Given central role of microglia in pathogenesis inflammation-related delirium, we investigated temporal dynamics neurobehavioral changes and microglial responses, following lipopolysaccharide (LPS, 200 μg/kg) administration young old male C57BL/6 mice. Although a similar illness trajectory across 48 h post-treatment (HPT) was observed both age groups, old-LPS mice exhibited...

Cone photoreceptors are the primary initiator of visual transduction in human retina. Dysfunction or death rod precedes cone loss many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for survival. Rod differentiation homeostasis dependent on basic motif leucine zipper transcription factor neural retina (NRL). The Nrl ( −/− ) mice results with predominantly S-opsin-containing cones that exhibit molecular functional characteristics wild-type cones. Here,...

Purpose.: Immune and vascular alterations in the choroid are implicated age-related macular degeneration (AMD). As choroidal immune cells incompletely understood with regard to their physiology interactions vessels, we examined associations between myeloid components of young aged mice. Methods.: Albino CX3CR1GFP/+ transgenic mice, whose possess green fluorescence, were perfused intraluminally vital dye DiI label vessels. The distribution, morphology, behavior, resident using time-lapse live...