Abnormal centrifugal axons in streptozotocin-diabetic rat retinas

PURPOSE. To characterize the effects of diabetes on the expression of histi dine decarboxylase mRNA and on the morphology of the histaminergic centrifu gal axons in the rat retina. METHODS. Rats were made diabetic by streptozotocin. After 3 months, retinal histidine decarboxylase expression was analyzed by in situ hybridization i n radial sections. Flatmount retinas from a second group of rats were label ed with an antiserum to histamine or an antibody to phosphorylated neurofil ament. protein. RESULTs. Histidine decarboxylase mRNA was expressed in cells in the inner a nd outer nuclear layers of diabetic retinas, but not in normal retinas. How ever, immunoreactive (IR) histamine was not localized to perikarya in eithe r the normal or the diabetic retinas. Instead, a population of centrifugal axons was labeled. These axons emerged from the optic disc and had varicose terminal branches in the inner plexiform layer (IPL) of the peripheral ret ina. Some branches ended on large retinal blood vessels and others in dense clusters in the IPL. In rats with streptozotocin-induced diabetes, the cen trifugal axon terminals developed many large swellings that contained neuro filament immunoreactivity; these swellings were rare in normal retinas. CONCLUSIONS. Diabetes perturbs the retinal histaminergic system, causing in creases in histidine decarboxylase mRNA expression in neurons or glia and a bnormal focal swellings on the centrifugal axons.