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Andrey V Dmitriev, Desmond Henderson, Jennifer C Lau, Robert A Linsenmeier; Retinal Acidosis at an Early Stage of Diabetes in the Rat. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1049.
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To determine the extent of acidosis in the retina of 1 month diabetic rats.
Double-barreled H+-selective microelectrodes were used to measure profiles throughout the retina of dark-adapted intact Long-Evans rats. Profiles were measured in age-matched normal rats and diabetic rats 1 month after intraperitoneal injection of streptozocin. The microelectrode penetrated to the choroid in steps and then was slowly withdrawn to generate a profile. The rats were anesthetized during preparation with 2.5-3% isoflurane/35% O2 and during recordings with urethane. The intraretinal electroretinogram (ERG) was evaluated to determine the retinal depth of the electrode and the condition of the retina. Absolute values of [H+] were obtained by assuming that the arterial [H+] measured just before or after each profile was the same as [H+] in the choroid.
Blood glucose at the time of measurements was 147±10 mg/dl (mean±SEM) in control rats and 342±11 mg/dl in diabetics. The outer nuclear layer was the most acidic region of the retina. Control rats had an average [H+] of 37.3 ± 0.5 nM at the choroid, 57.2 ± 1.0 nM (pH=7.24) averaged over the outer nuclear layer, and 42.5 ± 0.8 in the vitreous (n=12 profiles from 4 rats). For 1 month diabetic rats the corresponding values were 40.6 ± 0.6 nM at the choroid, 65.8 ± 1.4 nM in the outer nuclear layer (pH=7.18), and 45.4 ± 2.0 in the vitreous (n=18 profiles from 6 rats). The increase of [H+] in diabetic retinas compared to control was statistically significant (P=0.001; t-test). Additionally, H+ profiles in diabetic retinas were more variable in shape than those in control animals. The ‘shape index’ (([H+]retina-[H+]choroid)/([H+]retina-[H+]vitreous)) was about the same for the diabetic and control groups (1.38 and 1.39, correspondingly) but the standard deviation of this parameter was ~3 times larger for diabetics (± 0.61) than for control (± 0.23).
Retinal acidosis begins to develop at an early stage of diabetes (1 month) in rats. The elevation of [H+] in the retina is expected because of increased glucose in the blood. Also the shape of [H+] profiles, which are generally uniform in healthy rat retinas, are more variable in diabetics, hinting at a disruption of retinal H+ regulation due to a progressive abnormality in the retinal circulation and/or cellular pH regulatory processes.
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