Abstract

FR.14.07

Glial reactivity and alterations in blood vessels in the diabetic retina

Rungger-Brändle E., Conti A., Dosso A. A.
Cell Biology Laboratory University Eye Clinic, HUG, Geneva/CH

Aim: Vasculopathy and glial reactivity are hallmarks of early diabetic retinopathy and are common also to other angiopathies such as Alzheimer’s disease (AD). Insulin intervenes at several steps of amyloid protein processing and degradation, and studies have indeed shown an increased risk of diabetes type 2 patients to develop AD. Amyloid deposits are toxic to vascular cells. Yet, in diabetes type 1, it is unknown whether or how insulin deficiency affects the amyloid metabolism in the retina. We will report on preliminary observations collected in a rat model with diabetes type 1.
Methods: Amyloid precursor protein (APP) and its cleavage product amyloid-beta were localized by immunocytochemistry and confocal microscopy in retinas of streptozotocin-induced rats, a model of diabetes type 1. Protein and mRNA levels of amyloid precursor protein and several enzymes involved in amyloid-beta production were determined by Western blot and real-time PCR.
Results: APP is strongly enriched in Müller cells and tends to be enhanced in diabetic animals. Evaluation of mRNA levels of APP and its degradation enzymes is in progress. Amyloid-beta is expressed in synapses and ganglion cells, in perivascular regions, and at the inner blood-retinal barrier, where it colocalizes with occludin. These deposits tend to be increased with age and diabetes.
Conclusions: The specific localization of APP in Müller cells suggests that they are a major source of this protein. Deposits of amyloid-beta may have an influence on synaptic function and on the permeability of the inner blood retinal barrier.

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