Rod phototransduction and light signal transmission during type 2 diabetes
Authors: Becker Silke , Carroll Lara S. , Vinberg Frans 
Published: January 2020

Objective

Diabetic retinopathy is a major complication of diabetes recently associated with compromised photoreceptor function. Multiple stressors in diabetes, such as hyperglycemia, oxidative stress and inflammatory factors, have been identified, but systemic effects of diabetes on outer retina function are incompletely understood. We assessed photoreceptor physiology in vivo and in isolated retinas to better understand how alterations in the cellular environment compared to intrinsic cellular/molecular properties of the photoreceptors, affect light signal transduction and transmission in the retina in chronic type 2 diabetes.

Research Design and Methods

Photoreceptor function was assessed in BKS.Cs-Dock7m +/+ Lepr db/J mice, using homozygotes for Leprdb as a model of type 2 diabetes and heterozygotes as non-diabetic controls. In vivo electroretinogram (ERG) was recorded in dark adapted mice at both 3 and 6 months of age. For ex vivo ERG, isolated retinas were superfused with oxygenated Ames’ media supplemented with 30 mM glucose or mannitol as iso-osmotic control and electrical responses to light stimuli were recorded.

Results

We found that both transduction and transmission of light signals by rod photoreceptors were compromised in 6 month old (n=9-10 eyes from 5 animals,*** p<001) but not in 3 month old diabetic mice in vivo (n=4-8 eyes from 2-4 animals). In contrast, rod signaling was similar in isolated retinas from 6 month old control and diabetic mice under normoglycemic conditions (n=11). Acutely elevated glucose ex vivo increased light-evoked rod photoreceptor responses in control mice (n=11, *** p<0.001), but did not affect light responses in diabetic mice (n=11).

Conclusions

Our data suggest that long-term diabetes does not irreversibly change the ability of rod photoreceptors to transduce and mediate light signals. However, type 2 diabetes appears to induce adaptational changes in the rods that render them less sensitive to increased availability of glucose.

Significance of this study

What is already known about this subject?

Retinal neuronal dysfunction in diabetic retinopathy frequently precedes microvascular changes. Damage to photoreceptors has been reported, although the literature is not entirely conclusive, and the underlying mechanisms and reversibility of photoreceptor dysfunction in diabetes remain unknown.

What are the new findings?

We confirm that retinal function is impaired in vivo in diabetic mice, but report normal function of the isolated diabetic retina under optimal physiological conditions. However, elevated glucose concentrations augment photoreceptor function in the isolated non-diabetic retina, whereas this response is impaired by long-term diabetes.

How might these results change the focus of research or clinical practice?

Our results clarify that photoreceptor function is not irreversibly damaged and that systemic factors may suppress photoreceptor function in diabetic mice in vivo. The consequences of altered glucose handling in long-term diabetic photoreceptors remain to be evaluated.