Telomerase in choroidal neovascularization

摘要 眼部血管生成异常是多种疾病导致灾难性视力丧失的基础 包括新生血管性老年性黄斑变性(NvAMD)、增殖性糖尿病 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 抗血管内皮生长因子疗法彻底改变了此类疾病的管理，这些药物遭受 几个路障。长时间的抗血管内皮生长因子治疗伴随着严重的风险和 尽管接受了治疗，但仍有相当数量的患者出现视力丧失。因此，新的 深入了解促进视网膜血管生成的分子机制是必要的 开发更有效的治疗方法。实验室最近的研究发现了一种 实验性脉络膜新生血管小鼠模型端粒酶促血管生成活性研究 (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，以检验这一假设 端粒酶是异常眼血管生成的重要介质。为此，雇用 激光损伤诱导的小鼠脉络膜新生血管模型，我们将严格定义 并检测端粒酶的促血管生成活性是否及如何促血管生成 端粒酶和血管内皮细胞生长因子信号转导机制相互融合。总体而言，我们预计 这项研究不仅将为端粒酶在眼血管生成中的作用提供新的见解， 也为检验端粒酶生物学之间的协同作用开辟了新的研究途径 眼球血管生成和视网膜血管病变背景下的多发性致盲疾病。

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.