Müller glia in disease and stress

血管内皮生长因子是湿性年龄相关性疾病的主要致病因素 黄斑变性(AMD)和糖尿病视网膜病变(DR)是导致老年人失明的主要原因 我们。对湿性AMD和DR的深入研究导致了抗血管内皮生长因子策略的发展 治疗这些疾病中的血-视网膜屏障(BRB)破坏。要调查功能 血管内皮生长因子信号转导在视网膜主要支持细胞--Müller胶质细胞中的意义 受体-2(VEGFR2)在小鼠视网膜中观察到Müler细胞明显丢失，视网膜加速 神经元变性和两种神经营养因子的大幅减少：脑源性 视网膜中神经营养因子和胶质细胞源性神经营养因子的表达 糖尿病/缺氧。在本研究中，我们将确定血管内皮生长因子信号转导的机制。 Müler细胞活性，评估血管内皮生长因子信号在神经营养因子产生中的意义， 并探讨补充神经营养素对糖尿病患者神经保护的治疗潜力 低氧动物。我们的研究将有助于建立治疗的一般策略的基础。 DR和其他缺氧性视网膜疾病的神经元病理并为 穆勒神经胶质细胞是这些疾病中神经保护剂的细胞来源。

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.