Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Cells. 2022 Nov 24;11(23):3755. doi: 10.3390/cells11233755.
The main degenerative diseases of the retina include macular degeneration, proliferative vitreoretinopathy, retinitis pigmentosa, and glaucoma. Novel approaches for treating retinal diseases are based on cell replacement therapy using a variety of exogenous stem cells. An alternative and complementary approach is the potential use of retinal regeneration cell sources (RRCSs) containing retinal pigment epithelium, ciliary body, Müller glia, and retinal ciliary region. RRCSs in lower vertebrates in vivo and in mammals mostly in vitro are able to proliferate and exhibit gene expression and epigenetic characteristics typical for neural/retinal cell progenitors. Here, we review research on the factors controlling the RRCSs' properties, such as the cell microenvironment, growth factors, cytokines, hormones, etc., that determine the regenerative responses and alterations underlying the RRCS-associated pathologies. We also discuss how the current data on molecular features and regulatory mechanisms of RRCSs could be translated in retinal biomedicine with a special focus on (1) attempts to obtain retinal neurons de novo both in vivo and in vitro to replace damaged retinal cells; and (2) investigations of the key molecular networks stimulating regenerative responses and preventing RRCS-related pathologies.
视网膜的主要退行性疾病包括黄斑变性、增生性玻璃体视网膜病变、色素性视网膜炎和青光眼。治疗视网膜疾病的新方法基于使用各种外源性干细胞的细胞替代疗法。另一种替代和互补的方法是潜在地使用含有视网膜色素上皮、睫状体、Müller 胶质细胞和视网膜睫状区的视网膜再生细胞来源（RRCS）。体内的低等脊椎动物和体外的哺乳动物中的 RRCS 能够增殖，并表现出神经/视网膜细胞祖细胞的典型基因表达和表观遗传特征。在这里，我们回顾了控制 RRCS 特性的因素研究，例如细胞微环境、生长因子、细胞因子、激素等，这些因素决定了 RRCS 相关病变的再生反应和变化。我们还讨论了如何将 RRCS 的分子特征和调控机制的现有数据转化为视网膜生物医学，特别关注 (1) 试图在体内和体外获得新的视网膜神经元，以替代受损的视网膜细胞；和 (2) 研究刺激再生反应和防止 RRCS 相关病变的关键分子网络。
