Müller glia in disease and stress

血管内皮生长因子（VEGF）是湿性衰老相关性血管紧张素Ⅱ的主要致病因子， 黄斑变性（AMD）和糖尿病性视网膜病变（DR）， 我们对湿性AMD和DR的深入研究导致了抗VEGF策略的发展， 治疗这些疾病中的血视网膜屏障（BRB）破坏。为了研究功能性 VEGF信号在视网膜主要支持细胞Müller神经胶质中的意义，我们破坏了VEGF 受体-2（VEGFR 2），并观察到Müller细胞的显着损失，加速视网膜 神经元变性，以及两种神经营养因子的大量减少：脑源性 神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）在视网膜中的表达。 糖尿病/缺氧。在本研究中，我们将确定VEGF信号介导的机制， Müller细胞活力，评价VEGF信号传导在神经营养素产生中的意义， 并探讨神经营养素对糖尿病或糖尿病患者神经保护的治疗潜力。 缺氧动物我们的研究将有助于建立一个一般性的战略，以治疗的基础 DR和其他缺氧性视网膜疾病中的神经元病理学，并为 Müller胶质细胞作为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.