Light sensitivity of ON alpha retinal ganglion cells decreased in four-week diabetic mouse retina

Abstract

Purpose : Retinal ganglion cells (RGCs) are particularly vulnerable to the effects of diabetic retinopathy, one of the complications of Diabetes Mellitus (DM). This study will investigate the impact of high blood glucose levels on the light sensitivities of αRGCs.

Methods : 8-10w C57BL6 mice of both sexes were randomly separated into Streptozotocin (STZ)-treated and control groups. A single-dose intraperitoneal injection of 200mb/kg STZ or PBS was given. Serum glucose was measured 7 days and 4 weeks after injection. The mice of which non-fasting serum glucose exceed 350 mb/dL were determined as DM. Optokinetic test and Electroretinogram were tested before patch clamp. Isolated retinas were stimulated with increased intensities of green light ranged from 1464 to 2.02×10⁶ photons/ (um² sec). The light-invoked spike response, excitatory and inhibitory postsynaptic currents (EPSCs /IPSCs) response of ON and OFF αRGCs were recorded.

Results : The glucose levels in the diabetic mice were significantly increased by STZ injection at 7 days (p=0.004), and 4 weeks (p<0.0001, DM: 34 ± 0, n=5, Con: 13.88 ± 1.754, n=4). The contrast sensitivity of the mice measured with optokinetic test did not show a significant difference between two groups (p=0.24; DM: n=10; Con: n=8). In ERG, the positive scotopic threshold response (pSTR) at the -4.32 log cds/m² showed significant higher amplitude in DM group (p=0.008; DM: n=8, Con: n=6), but no differences were observed in other scotopic threshold stimuli, a wave, and b wave (p>0.05). The ON αRGCs in DM mice showed higher light sensitivity thresholds than control in spike responses (p=0.03; DM: 3433 ± 2346, n=6; Con: 359.7 ± 163.7 photons/ (um² sec), n=4), and EPSCs (p=0.02; DM: 6040 ± 3901, n=4; Con: 504 ± 132, n=4), while not in IPSCs (p>0.05). For OFF αRGCs, the light sensitivity thresholds of the two groups did not show differences in spike response, EPSCs, and IPSCs (p>0.05).

Conclusions : There is no significant difference in contrast sensitivity and visual function in the four-week DM mice model compared with these in control mice. However, the sensitivity of light-evoked spike activities and EPSCs of ON αRGCs decreased in diabetic group. Therefore, ON αRGCs might be more vulnerable and sensitive to neuronal damage before the visual function loss in the diabetic mouse retinas.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.