Effects of early diabetes on light-induced pH changes in the rat retina.

Abstract

Purpose: To determine whether light-induced pH changes are altered in the retina of rats at early stages of diabetes.

Methods: Double-barreled H⁺-selective microelectrodes were used to measure local extracellular [H⁺] changes in the retina of dark-adapted anesthetized Long-Evans rats. Recordings were performed in control and diabetic rats 1 to 2 months after intraperitoneal injection of vehicle or streptozocin. The microelectrode advanced in steps of 30 μm throughout the retina from vitreal surface to retinal pigment epithelium and then to the choroid, recording changes in [H⁺] evoked by light stimulation.

Results: Light stimulation evoked changes of [H⁺] with amplitudes of about 5 nM. Throughout the retina, there was a transient initial acidification for 300-500 msec followed by steady alkalinization, although amplitudes and kinetics of these components were variable in different retinal layers. The light-induced [H⁺] changes in early diabetic rats were not significantly different from those recorded in control rats. However, a striking difference between light-induced [H⁺] changes in controls and diabetics was observed in the choroid, in the thin layer (10-15 μm) near the basal membrane of the retinal pigment epithelium (RPE). In control rats, choroidal [H⁺] either decreased (in ~1/3 of the cases) or practically did not change (in ~2/3 of the cases). In contrast, diabetic rats demonstrated either an increase (in half of the cases) or no changes (in another half of the cases) in choroidal [H⁺]. Interestingly, elevation of blood glucose in control rats from 150 to 450-500 mg/dL could mimic that effect, and, atypically for control animals, increases in choroidal [H⁺] were then recorded. In both diabetics and controls, light caused an increase in [H⁺] within the RPE cell layer itself.

Conclusions: The rapid increases in [H⁺] observed here are too fast, and in the wrong direction, to be caused by light-evoked changes in metabolism, and are likely to reflect changes in H⁺ or HCO₃^- membrane transport. These data demonstrate that the regulation of H⁺ is altered at an early stage of diabetes in rats. The RPE, which is well equipped to control [H⁺] in the surrounding region, probably contributes to these alterations. The data also suggest that the active participation of choroidal blood supply in stabilization of [H⁺] could be partially compromised in early diabetic rats.