School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong.
Int J Mol Sci. 2022 Nov 1;23(21):13366. doi: 10.3390/ijms232113366.
Diabetic retinopathy (DR) was identified as a leading cause of blindness and vision impairment in 2020. In addition to vasculopathy, DR has been found to involve retinal neurons, including amacrine cells and retinal ganglion cells. Despite possessing features that are susceptible to diabetic conditions, photoreceptor cells have received relatively little attention with respect to the development of DR. Until recently, studies have suggested that photoreceptors secret proinflammatory molecules and produce reactive oxygen species that contribute to the development of DR. However, the effect of hyperglycemia on photoreceptors and its underlying mechanism remains elusive. In this study, the direct effect of high glucose on photoreceptor cells was investigated using a 661w photoreceptor-like cell line. A data-independent sequential window acquisition of all theoretical mass spectra (SWATH)-based proteomic approach was employed to study changes induced by high glucose in the proteomic profile of the cells. The results indicated that high glucose induced a significant increase in apoptosis and ROS levels in the 661w cells, with mitochondrial dysfunction among the major affected canonical pathways. The involvement of mitochondrial dysfunction was further supported by increased mitochondrial fission and reduced mitochondrial bioenergetics. Collectively, these findings provide a biological basis for a possible role of photoreceptors in the pathogenesis of DR.
糖尿病性视网膜病变（DR）在 2020 年被确定为导致失明和视力损害的主要原因。除了血管病变，DR 还被发现涉及视网膜神经元，包括无长突细胞和视网膜神经节细胞。尽管感光细胞具有易受糖尿病影响的特征，但在 DR 的发展过程中，它们受到的关注相对较少。直到最近，研究表明感光细胞会分泌促炎分子并产生活性氧物质，从而促进 DR 的发展。然而，高血糖对感光细胞的影响及其潜在机制仍不清楚。在这项研究中，使用 661w 感光细胞样细胞系研究了高葡萄糖对感光细胞的直接影响。采用基于数据独立的顺序窗口采集所有理论质谱（SWATH）的蛋白质组学方法研究了高葡萄糖对细胞蛋白质组图谱的诱导变化。结果表明，高葡萄糖诱导 661w 细胞凋亡和 ROS 水平显著增加，线粒体功能障碍是主要受影响的经典途径之一。线粒体功能障碍的参与还得到了线粒体裂变增加和线粒体生物能量学降低的支持。综上所述，这些发现为感光细胞在 DR 发病机制中的可能作用提供了生物学基础。
