Diminished light sensitivities of ON alpha retinal ganglion cells observed in a mouse model of hyperglycemia

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. •The key question is to explore the impact of hyperglycemia on retinal ganglion cells (RGCs) in mouse retinas before the appearance of any vascular signs.•The hyperglycemic mouse model was established through the administration of streptozotocin (STZ) via intraperitoneal injection.•In this model, a reduction in light sensitivity was observed in ON alpha(α) RGCs, but not in OFF αRGCs. This finding suggests that ON αRGCs may be more susceptible to changes in the retinal microenvironment induced by elevated blood sugar levels.