Retinal signaling under dark-adapted conditions is perturbed during early diabetes. Additionally, dopamine, the main neuromodulator of retinal light adaptation, is diminished in diabetic retinas. However, it is not known if this dopamine deficiency changes how the retina responds to increased light or dopamine. Here we determine whether light adaptation is impaired in the diabetic retina, and investigate potential mechanism(s) of impairment. Diabetes was induced in C57BL/6J male mice via 3 intraperitoneal injections of streptozotocin (75 mg/kg) and confirmed by blood glucose levels more than 200 mg/dL. After 6 weeks, whole-cell recordings of light-evoked and spontaneous inhibitory postsynaptic currents (IPSCs) or excitatory postsynaptic currents (EPSCs) were made from rod bipolar cells and ON sustained ganglion cells, respectively. Light responses were recorded before and after D1 receptor (D1R) activation (SKF-38393, 20 μM) or light adaptation (background of 950 photons·μm⁻² ·s⁻¹). Retinal whole mounts were stained for either tyrosine hydroxylase and activated caspase-3 or GAD65/67, GlyT1 and RBPMS and imaged. D1R activation and light adaptation both decreased inhibition, but the disinhibition was not different between control and diabetic rod bipolar cells. However, diabetic ganglion cell light-evoked EPSCs were increased in the dark and showed reduced light adaptation. No differences were found in light adaptation of spontaneous EPSC parameters, suggesting upstream changes. No changes in cell density were found for dopaminergic, glycinergic or GABAergic amacrine cells, or ganglion cells. Thus, in early diabetes, ON sustained ganglion cells receive excessive excitation under dark- and light-adapted conditions. Our results show that this is not attributable to loss in number or dopamine sensitivity of inhibitory amacrine cells or loss of dopaminergic amacrine cells.

在早期糖尿病期间，暗适应条件下的视网膜信号受到干扰。此外，多巴胺（视网膜光适应的主要神经调节剂）在糖尿病视网膜中减少。然而，目前尚不清楚这种多巴胺缺乏是否会改变视网膜对增加的光或多巴胺的反应。在这里，我们确定糖尿病视网膜中的光适应是否受到损害，并研究损害的潜在机制。通过 3 次腹腔注射链脲佐菌素 (75 mg/kg) 在 C57BL/6J 雄性小鼠中诱导糖尿病，并通过血糖水平超过 200 mg/dL 进行确认。6 周后，光诱发和自发抑制性突触后电流 (IPSC) 或兴奋性突触后电流 (EPSC) 的全细胞记录分别由杆状双极细胞和 ON 持续神经节细胞制成。⁻² ·s ⁻¹）。视网膜整个支架针对酪氨酸羟化酶和活化的 caspase-3 或 GAD65/67、GlyT1 和 RBPMS 进行染色并成像。D1R 激活和光适应都降低了抑制作用，但对照和糖尿病杆状双极细胞之间的去抑制作用没有差异。然而，糖尿病神经节细胞光诱发的 EPSCs 在黑暗中增加并且表现出对光适应的降低。在自发 EPSC 参数的光适应中没有发现差异，表明上游发生了变化。没有发现多巴胺能、甘氨酸能或 GABA 能无长突细胞或神经节细胞的细胞密度变化。因此，在早期糖尿病中，ON 持续神经节细胞在暗适应和光适应的条件下会受到过度激发。