Impacts of Diabetes on Retinal Neurocircuitry: Investigating Physiological Responses of ON and OFF Pathways in Db/db Mice Retinas

Abstract

Purpose: : Diabetic retinopathy is associated with alterations in neuronal function before the onset of clinical vascular disease. To quantitatively evaluate early influences of diabetic retinopathy upon ON and OFF neural pathways, we investigated physiological response properties of ON-center and OFF-center retinal ganglion cells (RGCs) in db/db mice.

Methods: : db/db mice aged of 8, 12, and 20 wks were used in this experiment. RGCs were stained with two drops of 0.002% Acridine orange. Visual stimuli were generated by programming a graphic card. Single-unit responses from RGCs in a superfused, flattened eyecup preparation were recorded in vitro. In addition, simultaneous recordings from ON and OFF RGC pairs at the same retinal locations were carried out.

Results: : Visual responses of ON and OFF RGCs (n=40) showed different time course of functional deterioration. At 8 wks (ON: n=5; OFF: n=6) and 12 wks (ON: n=8; OFF: n=5), there were progressive losses in contrast and luminance sensitivities. Nevertheless, there was no marked difference in visual response deficiency among ON and OFF cells. At 20 wks, however, there were clear distinctions between these two channels. Simultaneous recordings from ON and OFF RGC pairs at the same retinal locations revealed that ON cells had higher luminance and contrast threshold than OFF cells. Furthermore, the most frequently recorded cells were OFF RGCs (ON: n=5; OFF: n =11) while encountered ON cells exhibited weak and irregular visual response patterns.

Conclusions: : Diabetic retinopathy induced retinal degeneration alters RGC contrast and visual sensitivity functions. At 20 wks, ON and OFF RGCs exhibit different tolerance in response to diabetic retinal degeneration. ON channel appears more susceptible to diabetes induced injury whereas OFF channel is less vulnerable. The present study offers evidence for objective evaluation of retinal visual function deterioration at different stages of diabetic retinopathy.

Keywords: diabetic retinopathy • electrophysiology: non-clinical • ganglion cells