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Andrey V Dmitriev, Desmond Henderson, Robert A Linsenmeier; Diabetes compromises pH control in the rat retina.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):108.
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© 2017 Association for Research in Vision and Ophthalmology.
To determine whether the ability of the rat retina to control its pH is affected by diabetes.
Double-barreled H+-selective microelectrodes were used to measure local extracellular [H+] in the retina of dark-adapted anesthetized Long-Evans rats. Recordings were performed in control and diabetic rats 1 to 6 months after intraperitoneal injection of vehicle or streptozocin. The microelectrode penetrated to the choroid in steps and then was slowly withdrawn to generate a profile that characterized transretinal H+ distribution. Two manipulations – increasing of blood glucose and injection of carbonic anhydrase blocker dorzolamide (DZM) – were used to interfere with retinal pH regulation, and results of these disturbances in control and diabetic retinas were compared. Averaged data are presented as mean±s.e., n –number of H+-profiles.
As we have shown previously diabetic retinas often, but not always, were more acidic than controls. For these experiments we intentionally selected diabetic animals with mildly affected retinal pH. Adding intravenous glucose in control animals elevated plasma glucose from 144.2±10.0 (n=21) to 486.2±13.0 (n=22) mg/dL, but had almost no effect on the amplitude of the H+-profiles in the retina (37.8±1.9 and 35.0±2.8 nM, respectively). In contrast, similar injections of glucose in diabetic rats significantly increased both the glucose level (from 333.6±12.6 to 554.3±12.1 mg/dL, n = 18 and 19), and the amplitude of the H+-profiles (from 31.4±1.7 to 49.9±4.9 nM). The spatial heterogeneity of the H+ distribution in diabetic retinas that have been described earlier was also enhanced by elevating blood glucose. Suppression of carbonic anhydrase by DZM dramatically increased the amplitude of H+-profiles in control (from 36.5±1.6 to 126.9±9.4 nM, n = 17 and 13) as well as in diabetic retinas (from 44.3±3.3 to 129.4±13.3nM, n = 30 and 24). However, the duration of DZM application had an opposite effect in control and diabetic retinas. In controls, the strongest effect was recorded within 10 min after the injection, and then the effect slightly decreased. In diabetics, the effect of DZM tended to increase with time, and after 2 hours could be 2-3 times larger than at the beginning.
The data indicate that during development of diabetes the control over retinal pH is partly compromised so that diabetics are less able to withstand conditions that perturb retinal pH.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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