Karpagavalli Muthuramalingam, Sindal Manavi D, Arunachalam Jayamuruga Pandian, Chidambaram Subbulakshmi
Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605 014, India.
Retina Services, Aravind Eye Hospital, Puducherry, India.
Exp Eye Res. 2025 Feb;251:110236. doi: 10.1016/j.exer.2025.110236. Epub 2025 Jan 10.
Diabetic Retinopathy (DR), a leading complication of diabetes mellitus, has long been considered as a microvascular disease of the retina. However, recent evidence suggests that DR is a neurovascular disease, characterized by the degeneration of retinal neural tissue and microvascular abnormalities encompassing ischemia, neovascularization, and blood-retinal barrier breakdown, ultimately leading to blindness. The intricate relationship between the retina and vascular cells constitutes a neurovascular unit, a multi-cellular framework of retinal neurons, glial cells, immune cells, and vascular cells, which facilitates neurovascular coupling, linking neuronal activity to blood flow. These interconnections between the neurovascular components get compromised due to hyperglycemia and are further associated with the progression of DR early on in the disease. As a result, therapeutic approaches are needed to avert the advancement of DR by acting at its initial stage to delay or prevent the pathogenesis. Non-coding RNAs (ncRNAs) such as microRNAs, piwi-interacting RNAs, and long non-coding RNAs regulate various cellular components in the neurovascular unit. These ncRNAs are key regulators of neurodegeneration, apoptosis, inflammation, and oxidative stress in DR. In this review, research related to alterations in the expression of ncRNAs and, correspondingly, their effect on the disintegration of the neurovascular coupling will be discussed briefly to understand the potential of ncRNAs as therapeutic targets for treating this debilitating disease.
糖尿病视网膜病变（DR）是糖尿病的主要并发症，长期以来一直被视为视网膜的微血管疾病。然而，最近的证据表明，DR是一种神经血管疾病，其特征是视网膜神经组织退化和微血管异常，包括缺血、新生血管形成和血视网膜屏障破坏，最终导致失明。视网膜与血管细胞之间的复杂关系构成了一个神经血管单元，这是一个由视网膜神经元、神经胶质细胞、免疫细胞和血管细胞组成的多细胞框架，它促进神经血管耦合，将神经元活动与血流联系起来。由于高血糖，神经血管成分之间的这些相互联系受到损害，并在疾病早期进一步与DR的进展相关。因此，需要采取治疗方法，通过在疾病初期采取行动来延缓或预防发病机制，从而避免DR的进展。非编码RNA（ncRNA），如微小RNA、piwi相互作用RNA和长链非编码RNA，调节神经血管单元中的各种细胞成分。这些ncRNA是DR中神经退行性变、细胞凋亡、炎症和氧化应激的关键调节因子。在这篇综述中，将简要讨论与ncRNA表达改变相关的研究，以及相应地它们对神经血管耦合解体的影响，以了解ncRNA作为治疗这种使人衰弱疾病的治疗靶点的潜力。
