Non-uniform distribution of lesions and biochemical abnormalities within the retina of diabetic humans

Abstract

Objective: Microaneurysms, acellular capillaries, pericyte ghosts, and thickening of retinal capillary basement membrane are characteristic of diabetic retinopathy, and are believed to be sequelae of excessive blood glucose. Previous studies by us in dogs demonstrated that lesions of diabetic retinopathy were not uniformly distributed across the retina, but were significantly more numerous in the superior/temporal areas of the retina. In the present study, the distribution of these lesions and the biochemical abnormalities postulated to play a role in their pathogenesis have been evaluated in retinas collected at autopsy from diabetic patients.

Methods: Retinas were divided into quadrants (nasal, temporal, superior, inferior), the vasculature exposed by the trypsin-digest method, and the frequency of the lesions compared among the quadrants. Homogenates taken from the mid-retina of nasal and temporal quadrants of retina were used to explore regional differences in expression of Glut1, PKCbeta, and iNOS (Western blots) and caspases (enzymatic activity).

Results: Microaneurysms, acellular capillaries and pericyte ghosts were not uniformly distributed across the retina, and were significantly more numerous in the temporal retina than in the nasal retina (P < 0.05). In contrast, the thickness of retinal capillary basement membrane was not found to differ significantly across the retina. In our limited study, activity of the pro-inflammatory protease, caspase 1, was the only biochemical abnormality where there was both a significant diabetes-induced alteration in activity and also a significant difference between retinal quadrants. Expression of the glucose transporter, Glut1, was significanlty decreased in diabetes, but there was no significant difference in expression between the quadrants. Expression of iNOS was increased only in temporal retina in diabetes (but no significant difference between quadrants), and PKCbeta tended to be greater than normal in both temporal and nasal retina.

Conclusions: Retinal microvascular disease does not develop uniformly across the retina of diabetic patients, even though the different regions are exposed to the same level of hyperglycemia.