Telomerase in choroidal neovascularization

总结 异常的眼部血管生成是多种疾病导致的灾难性视力丧失的基础 包括新生血管性年龄相关性黄斑变性（nvAMD）、增殖性糖尿病性黄斑变性（proliferative diabetic macular degeneration， 视网膜病变（DR）、早产儿视网膜病变（ROP）和缺血性视网膜静脉阻塞。虽然 抗VEGF治疗已经彻底改变了这些疾病的管理， 几个路障。长期抗VEGF治疗伴随着严重的风险， 尽管进行了治疗，但仍有相当数量的患者经历视力丧失。因此，新 需要深入了解促进视网膜血管生成的分子机制， 开发更有效的治疗方法。实验室最近的研究已经确定了一种 小鼠实验性脉络膜新生血管模型中端粒酶活性的研究 （CNV）。这里提出的研究将建立在这些令人兴奋的新发现的基础上，以检验假设， 端粒酶是异常眼部血管生成的重要介质。为此，用人 激光损伤诱导的脉络膜新生血管的小鼠模型，我们将严格定义 端粒酶的促血管生成活性，并检查是否以及如何促血管生成 端粒酶和VEGF信号传导的机制会聚并相互作用。总的来说，我们预计 这项研究不仅将为端粒酶在眼部血管生成中的作用提供新的见解， 而且还为研究端粒酶生物学和细胞生物学之间的协同作用开辟了新的途径， 眼血管生成和视网膜血管病变的背景下，多种致盲性疾病。

SUMMARY Aberrant ocular angiogenesis underlies catastrophic loss vision due to multiple conditions including neovascular age-related macular degeneration (nvAMD), proliferative diabetic retinopathy (DR), retinopathy of prematurity (ROP), and ischemic retinal vein occlusion. Although anti-VEGF therapy has revolutionized the management of such disorders, the drugs suffer from several roadblocks. Prolonged anti-VEGF therapies are accompanied by serious risks and significant number of patients still experience vision loss despite treatment. Therefore, new insights into molecular mechanisms that promote angiogenesis in the retina are needed for the development of more effective therapies. Recent studies in the laboratory have identified a proangiogenic activity of telomerase in mouse model of experimental choroid neovascularization (CNV). Studies proposed here will build on these exciting new findings to test the hypothesis that telomerase is an important mediator of aberrant ocular angiogenesis. To this end, employing mouse model of laser injury-induced choroidal neovascularization, we will rigorously define proangiogenic activity of telomerase and examine whether and how the proangiogenic mechanisms of telomerase and VEGF signaling converge and interface. Overall, we anticipate that this study will not only provide new insights into the role of telomerase in ocular angiogenesis, but also usher in new avenues of research for examining the synergy between telomerase biology ocular angiogenesis and retinal vasculopathies in the context multiple blinding diseases.