Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast, UK.
Stem Cell Res Ther. 2022 Jul 30;13(1):388. doi: 10.1186/s13287-022-03073-x.
Diabetic retinopathy, a major complication of diabetes mellitus, is a leading cause of sigh-loss in working age adults. Progressive loss of integrity of the retinal neurovascular unit is a central element in the disease pathogenesis. Retinal ischemia and inflammatory processes drive interrelated pathologies such as blood retinal barrier disruption, fluid accumulation, gliosis, neuronal loss and/or aberrant neovascularisation. Current treatment options are somewhat limited to late-stages of the disease where there is already significant damage to the retinal architecture arising from degenerative, edematous and proliferative pathology. New preventive and interventional treatments to target early vasodegenerative and neurodegenerative stages of the disease are needed to ensure avoidance of sight-loss.
Historically, diabetic retinopathy has been considered a primarily microvascular disease of the retina and clinically it is classified based on the presence and severity of vascular lesions. It is now known that neurodegeneration plays a significant role during the pathogenesis. Loss of neurons has been documented at early stages in pre-clinical models as well as in individuals with diabetes and, in some, even prior to the onset of clinically overt diabetic retinopathy. Recent studies suggest that some patients have a primarily neurodegenerative phenotype. Retinal pigment epithelial cells and the choroid are also affected during the disease pathogenesis and these tissues may also need to be addressed by new regenerative treatments. Most stem cell research for diabetic retinopathy to date has focused on addressing vasculopathy. Pre-clinical and clinical studies aiming to restore damaged vasculature using vasoactive progenitors including mesenchymal stromal/stem cells, adipose stem cells, CD34 cells, endothelial colony forming cells and induced pluripotent stem cell derived endothelial cells are discussed in this review. Stem cells that could replace dying neurons such as retinal progenitor cells, pluripotent stem cell derived photoreceptors and ganglion cells as well as Müller stem cells are also discussed. Finally, challenges of stem cell therapies relevant to diabetic retinopathy are considered.
Stem cell therapies hold great potential to replace dying cells during early and even late stages of diabetic retinopathy. However, due to the presence of different phenotypes, selecting the most suitable stem cell product for individual patients will be crucial for successful treatment.
糖尿病视网膜病变是糖尿病的主要并发症，也是工作年龄段成年人视力丧失的主要原因。视网膜神经血管单元完整性的进行性丧失是疾病发病机制的核心要素。视网膜缺血和炎症过程驱动相互关联的病理学，如血视网膜屏障破坏、液体积累、神经胶质增生、神经元损失和/或异常新生血管形成。目前的治疗选择在某种程度上仅限于疾病的晚期，此时由于退行性、水肿和增生性病变，视网膜结构已经受到严重损害。需要新的预防和干预治疗方法来针对疾病的早期血管退行性和神经退行性阶段，以确保避免视力丧失。
糖尿病视网膜病变历史上被认为是视网膜的主要微血管疾病，临床上根据血管病变的存在和严重程度进行分类。现在已知神经退行性变在发病机制中起着重要作用。在临床前模型以及糖尿病患者中，甚至在一些人甚至在临床明显的糖尿病视网膜病变之前，已经记录到神经元的损失发生在早期阶段。最近的研究表明，一些患者具有主要的神经退行性表型。在疾病发病机制中，视网膜色素上皮细胞和脉络膜也受到影响，新的再生治疗也可能需要针对这些组织。迄今为止，大多数针对糖尿病视网膜病变的干细胞研究都集中在解决血管病变上。本文综述了旨在使用血管活性祖细胞（包括间充质基质/干细胞、脂肪干细胞、CD34 细胞、内皮祖细胞和诱导多能干细胞衍生的内皮细胞）恢复受损血管的临床前和临床研究。还讨论了可替代垂死神经元的干细胞，如视网膜祖细胞、多能干细胞衍生的光感受器和神经节细胞以及 Müller 干细胞。最后，考虑了与糖尿病视网膜病变相关的干细胞治疗的挑战。
干细胞治疗在糖尿病视网膜病变的早期甚至晚期阶段具有很大的潜力，可以替代垂死的细胞。然而，由于存在不同的表型，为每个患者选择最合适的干细胞产品对于成功治疗至关重要。
