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.
School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
Exp Eye Res. 2024 Nov;248:110113. doi: 10.1016/j.exer.2024.110113. Epub 2024 Sep 28.
This study aimed to investigate potential functional changes in retinal ganglion cells (RGCs) in a mouse model of hyperglycemia and explore possible therapeutic approaches. Hyperglycemia resembling type 1 diabetes mellitus (DM) was induced in C57BL/6 mice through intraperitoneal injection of streptozotocin (STZ). Blood glucose levels were confirmed to be elevated after 1 week and 4 weeks of injection. Mice with blood glucose levels above 350 mg/mL after 4 weeks of one-dose STZ injection were considered hyperglycemic. The light sensitivity of ON alpha (α) retinal ganglion cells (RGCs), not OFF αRGCs, was reduced in the hyperglycemic mouse model. The number of apoptotic cells, RGCs, and amacrine cells (ACs) remained unaffected at this stage. Similarly, the eletroretinogram (ERG) and optokinetic test results showed no significant differences. The application of picrotoxin (PTX) to block GABA receptors could increase the light sensitivity of ON αRGCs by 1 log unit in hyperglycemic mice. The results show that ON αRGCs may be more susceptible to microenvironmental changes caused by hyperglycemia than OFF αRGCs. This decline in light sensitivity may occur before cell apoptosis during the early stages of the hyperglycemic mouse model but has the potential to be reversed.
本研究旨在探讨高血糖症小鼠模型中视网膜神经节细胞（RGCs）的潜在功能变化，并探索可能的治疗方法。通过腹腔注射链脲佐菌素（STZ）在 C57BL/6 小鼠中诱导类似于 1 型糖尿病（DM）的高血糖症。注射后 1 周和 4 周确认血糖水平升高。单次 STZ 注射后 4 周血糖水平超过 350mg/mL 的小鼠被认为患有高血糖症。在高血糖小鼠模型中，ON alpha（α）视网膜神经节细胞（RGCs）的光敏感性降低，而非 OFF αRGCs。在这个阶段，凋亡细胞、RGCs 和无长突细胞（ACs）的数量没有受到影响。同样，眼电图（ERG）和视动测试结果也没有显示出显著差异。应用胡椒碱（PTX）阻断 GABA 受体可以使高血糖小鼠的 ON αRGCs 的光敏感性增加 1 个对数单位。结果表明，ON αRGCs 可能比 OFF αRGCs 更容易受到高血糖引起的微环境变化的影响。这种光敏感性下降可能发生在高血糖症小鼠模型的细胞凋亡之前，但有可能逆转。
