Müller glia in disease and stress

米勒神经胶质细胞在疾病和压力中的作用

• 批准号: 10163851
• 负责人: YUN Zheng LE
• 金额: $ 35.16万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163851
• 关键词: Address; Age related macular degeneration; Animals; Apoptosis; Biochemical; Biological Aging; Blindness; Blood Vessels; Blood-Retinal Barrier; Brain-Derived Neurotrophic Factor; Cell Line; Cell Survival; Clinical Trials; Consensus; Data; Dependovirus; Development; Diabetes Mellitus; Diabetic Retinopathy; Disease; Experimental Diabetes Mellitus; Extravasation; Eye diseases; Goals; Hypoxia; Inflammation; Investigational Therapies; KDR gene; Knockout Mice; Knowledge; Lesion; Mediating; Modeling; Molecular; Muller' s cell; Mus; Nerve Degeneration; Neurons; Neuroprotective Agents; Nonexudative age-related macular degeneration; Outcome; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Production; Public Health; Publications; Recombinant Proteins; Retina; Retinal Degeneration; Retinal Diseases; Retinopathy of Prematurity; Role; Safety; Signal Transduction; Source; Stress; Structure; Supporting Cell; Testing; Therapeutic; Thinness; Treatment Factor; United States National Institutes of Health; Ursidae Family; VEGFA gene; Vascular Endothelial Growth Factors; Virulence Factors; Vision; Visual Acuity; base; conditional knockout; density; design; diabetic; experimental study; glial cell-line derived neurotrophic factor; improved; in vivo; insight; mouse model; neuroprotection; neurotrophic factor; neutralizing antibody; pre-clinical; preservation; retinal neuron; small hairpin RNA

Vascular endothelial growth factor (VEGF) is a major pathogenic factor for wet age-related macular degeneration (AMD) and diabetic retinopathy (DR), leading causes of blindness in the US. Intensive studies on wet AMD and DR have led to the development of anti-VEGF strategy for treating blood-retina barrier (BRB) breakdown in these diseases. To investigate the functional significance of VEGF signaling in major retinal supporting cells, Müller glia, we disrupted VEGF receptor-2 (VEGFR2) in mice and observed a significant loss of Müller cells, accelerated retinal neuron degeneration, and a substantial reduction of two neurotrophins: brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in the retina in diabetes/hypoxia. In this study, we will determine the mechanism of VEGF signaling-mediated Müller cell viability, evaluate the significance of VEGF signaling in the production of neurotrophins, and explore therapeutic potential of supplying neurotrophins for neuroprotection in diabetic or hypoxic animals. Our study will contribute to the basis for establishing a general strategy to treat neuronal pathology in DR and other hypoxic retinal diseases and provide mechanistic insights for Müller glia as a cellular source of neuro-protectants in these diseases.

血管内皮生长因子（VEGF）是湿性衰老的主要致病因子