Changes in Corneal Innervation and Sensitivity and Acetylcholine-Mediated Vascular Relaxation of the Posterior Ciliary Artery in a Type 2 Diabetic Rat

Abstract

Corneal confocal microscopy is emerging as a clinical tool to evaluate the development and progression of diabetic neuropathy. The purpose of these studies was to characterize the changes in corneal sensitivity and innervation in a rat model of type 2 diabetes in relation to standard peripheral neuropathy endpoints. Assessment of diabetes-induced changes in corneal innervation and sensitivity in animal models will be important for determining the usefulness of corneal markers for preclinical studies to test potential new treatments for diabetic neuropathy. High-fat/low-dose streptozotocin diabetic rats were used to examine diabetes-induced changes in standard diabetic neuropathy endpoints and innervation of the cornea using confocal microscopy, corneal sensitivity using a Cochet-Bonnet esthesiometer, and vascular reactivity of the posterior ciliary artery. Compared with age-matched control rats, the induction of hyperglycemia in rats fed high-fat diets caused a decrease in nerve conduction velocity, thermal hypoalgesia, and intraepidermal nerve fiber profiles. In the cornea there was a decrease in corneal nerve fiber length and sensitivity. In addition, vascular relaxation in response to acetylcholine was decreased in the posterior ciliary artery. These studies suggest that in a type 2 diabetic rat model, changes in corneal nerve innervation and sensitivity occur that are consistent with changes seen in diabetic patients. Corneal sensitivity and innervation may be valuable endpoints for examining the potential treatments of diabetic neuropathy in preclinical studies.