CELL THERAPY FOR THE VASODEGENERATIVE STAGES OF DIABETIC RETINOPATHY

糖尿病视网膜病变是导致视力损害的主要原因。即使在目前的管理方案下，它也继续显著降低数百万受影响个人的生活质量。晚期糖尿病视网膜病变可以通过泛视网膜激光光凝在一定程度上得到治疗或遏制，但代价是对大片功能性视网膜造成损害。虽然正在开发一系列其他治疗方法，但大多数是针对终末期视网膜病变，未能解决以微血管细胞功能障碍和死亡为特征的早期病理。需要针对这些早期变化的新治疗方法，如细胞疗法，以修复/替换异常的糖尿病血管。这项研究将为开发新型干细胞奠定基础。通过将高度定义的骨髓源性内皮祖细胞(EPC)群体引入缺血视网膜来诱导治疗性血管生成的治疗。尽管在动物模型中，内皮祖细胞已被证明能有效地促进缺血心脏的血管重建，但它们在缺血视网膜中的确切作用仍不清楚。这项研究将彻底评估将不同的内皮祖细胞注射到缺血视网膜的玻璃体中所获得的任何好处。最近，有研究表明，来自1型糖尿病患者的内皮祖细胞功能紊乱，促进血管修复的能力降低。我们计划全面评估从糖尿病小鼠分离的EPC群体的功能，并将首次测试通过他汀类药物治疗糖尿病功能障碍的祖细胞来治愈它们的可能性。EPC是一组高度异质的细胞。根据注射到缺血视网膜的亚群，我们预计通过移植成为内皮细胞的前体细胞来促进血管修复。其他EPC亚群移植实际上可能通过成为炎症细胞而加剧视网膜损伤，这一反应需要确定。这项研究将明确定义具有促进血管恢复能力的细胞类型，重要的是，将评估细胞治疗后的视网膜功能。预计糖尿病小鼠的内皮祖细胞将出现功能障碍。我们期望从骨髓中获得这些细胞，在实验室中扩增它们，在移植前使用他汀类药物来纠正任何固有的缺陷。把它们变成捐赠者的眼睛。我们预计这种方法将解决糖尿病患者视网膜血管的进行性损害，并最终防止视力丧失。

Diabetic Retinopathy is a leading cause of visual impairment. Even with current management regimens it continues to significantly reduce the quality of life for millions of affected individuals. Late stages of diabetic retinopathy can be treated or contained to some extent by pan-retinal laser photocoagulation but at the expense of causing damage to large areas of functional retina. Although a range of other therapeutic approaches are being developed, most are directed to end-stage retinopathy and fail to address the early pathology characterised by microvascular cell dysfunction and death. New treatments focusing on these early changes such as cell therapies to repair/replace abnormal diabetic vasculature are needed. This study will establish the baselines for the development of a novel ?stem cell? therapy based on induction of therapeutic angiogenesis by introducing highly defined populations of bone marrow-derived endothelial progenitor cells (EPCs) into the ischemic retina. Although EPCs have been shown to promote effective revascularisation of ischemic hearts in animal models, their definitive role in the ischemic retina remains unclear. This study will thoroughly assess any benefit obtained from injecting distinct EPCs into the vitreous of ischemic retinas.Recently, it has been suggested that EPCs from type 1 diabetic patients are dysfunctional and display a reduced capacity to promote vascular repair. We plan to fully evaluate the function of EPC populations isolated from diabetic mice, and will test, for the first time, the possibility of healing diabetic dysfunctional progenitors by treating them with a statin.EPCs are a highly heterogeneous group of cells. Depending on the subpopulation that is injected into the ischemic retina we anticipate promoting vascular repair by transplanting progenitors that become endothelial cells. Other EPC subpopulation transplants could actually exacerbate retinal damage by becoming inflammatory cells and this response this is important to determine. This study will clearly define the cell type with the capacity to promote vascular recovery and, importantly, will evaluate retinal function after cell therapy.It is expected that endothelial progenitors from diabetic mice will be dysfunctional. We anticipate obtaining these cells from marrow, expanding them in the laboratory, correcting any inherent defect using statin treatment prior to ?transplanting? them into donor eyes. We expect that this approach will address the progressive retinal vascular damage that happens in diabetes and, ultimately, prevent vision loss.