Institute of Ophthalmology, University College London, London, UK.
Curr Eye Res. 2020 Mar;45(3):349-360. doi: 10.1080/02713683.2019.1669665. Epub 2019 Oct 2.
Retinal degeneration is a leading cause of untreatable blindness in the industrialised world. It is typically irreversible and there are few curative treatments available. The use of stem cells to generate new retinal neurons for transplantation purposes has received significant interest in recent years and is beginning to move towards clinical trials. However, such approaches are likely to be most effective for relatively focal areas of repair. An intriguing complementary approach is endogenous self-repair. Retinal cells from the ciliary marginal zone (CMZ), retinal pigment epithelium (RPE) and Müller glial cells (MG) have all been shown to play a role in retinal repair, typically in lower vertebrates. Among them, MG have received renewed interest, due to their distribution throughout (centre to periphery) the neural retina and their potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons. Triggering these innate self-repair mechanisms represents an exciting therapeutic option in treating retinal degeneration. However, these cells behave differently in mammalian and non-mammalian species, with a considerably restricted potential in mammals. In this short review, we look at some of the recent progress made in our understanding of the signalling pathways that underlie MG-mediated regeneration in lower vertebrates, and some of the challenges that have been revealed in our attempts to reactivate this process in the mammalian retina.
视网膜变性是工业化世界中不可治疗的失明的主要原因。它通常是不可逆转的，并且可用的治疗方法很少。近年来，使用干细胞生成用于移植的新的视网膜神经元引起了极大的关注，并开始向临床试验推进。然而，这种方法可能对相对集中的修复区域最有效。一种有趣的补充方法是内源性自我修复。睫状缘（CMZ）、视网膜色素上皮（RPE）和 Muller 胶质细胞（MG）的视网膜细胞都被证明在视网膜修复中发挥作用，通常在较低等的脊椎动物中。其中，MG 重新引起了人们的兴趣，因为它们分布在整个（中心到外周）神经视网膜中，并且在视网膜损伤后具有重新获得祖细胞样状态的潜力，能够增殖并产生新的神经元。触发这些内在的自我修复机制是治疗视网膜变性的一个令人兴奋的治疗选择。然而，这些细胞在哺乳动物和非哺乳动物物种中的行为不同，在哺乳动物中具有相当受限的潜力。在这篇简短的综述中，我们研究了一些关于理解 MG 在较低等脊椎动物中介导再生的信号通路的最新进展，以及在尝试重新激活哺乳动物视网膜中的这个过程时所揭示的一些挑战。
