High glucose and diabetes increase the release of [3H]-D-aspartate in retinal cell cultures and in rat retinas

Several evidences suggest that glutamate may be involved in retinal neurodegeneration in diabetic retinopathy (DR). For that reason, we investigated whether high glucose or diabetes affect the accumulation and the release of [3H]-D-aspartate, which was used as a marker of the glutamate transmitter pool. The accumulation of [3H]-D-aspartate did not change in cultured retinal neural cells treated with high glucose (30 mM) for 7 days. However, the release of [3H]-D-aspartate, evoked by 50 mM KCl, significantly increased in retinal cells exposed to high glucose. Mannitol, which was used as an osmotic control, did not cause any significant changes in both accumulation and release of [3H]-D-aspartate. In the retinas, 1 week after the onset of diabetes, both the accumulation and release of [3H]-D-aspartate were unchanged comparing to the retinas of agematched controls. However, after 4 weeks of diabetes, the accumulation of [3H]-D-aspartate in diabetic retinas decreased and the release of [3H]-Daspartate increased, compared to age-matched control retinas. These results suggest that high glucose and diabetes increase the evoked release of D-aspartate in the retina, which may be correlated with the hypothesis of glutamate-induced retinal neurodegeneration in DR