Physiological Response Properties of db/db Mice Retinal Ganglion Cells

Abstract

Purpose:: Diabetic retinopathy is a degenerative disease of the neural retina, associated with alternations in neuronal function before the onset of clinical vascular disease. To quantitatively evaluate the impact of retinopathy on retinal neural circuitry, we investigated physiological response properties of db/db mouse retinal ganglion cells.

Methods:: db/db mice aged of 8-52 weeks were used in this experiment. Retinal ganglion cells were either retrogradely labeled with 8% biotinylated dextran-conjugated methylrhodamine or stained with two drops of 0.002% Acridine orange. Visual stimuli were generated by programming a graphics card. Single-unit responses from ganglion cells in a superfused, flattened eyecup preparation were recorded in vitro under visual control.

Results:: Ganglion cell single unit visual response deteriorates slowly over the course of retinal neurocircuitry degeneration in db/db mice, with significant decreases in threshold sensitivity. Spatial frequency tuning and contrast responses were extremely weak in 52 weeks old db/db mice, paralleled by a progressive decline in signal-to-noise (S/N) ratio.

Conclusions:: The first definitive signs of degeneration in db/db mice neural retina are parallel decreases in ganglion cell threshold sensitivity and contrast responses, followed by deterioration in S-N ratio. This study offers important data for evaluating retinal visual function losses in diabetic retina.

Keywords: diabetic retinopathy • ganglion cells