Differences and similarities in development of corneal nerve damage and peripheral neuropathy and in diet-induced obesity and type 2 diabetic rats

• Published in: Investigative ophthalmology & visual science Vol. 55; no. 3; pp. 1222 - 1230
• Main Authors: Davidson, Eric P, Coppey, Lawrence J, Kardon, Randy H, Yorek, Mark A
• Format: Journal Article
• Language: English
• Published: United States The Association for Research in Vision and Ophthalmology 03.03.2014
• Subjects: Animals; Cell Count; Cornea - innervation; Cornea - pathology; Cornea - physiopathology; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - pathology; Dietary Fats - toxicity; Male; Microscopy, Confocal; Nerve Fibers - pathology; Obesity - complications; Obesity - pathology; Peripheral Nervous System Diseases - etiology; Peripheral Nervous System Diseases - pathology; Rats; Rats, Sprague-Dawley; Sensation; cornea; diabetic neuropathy; diabetes
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.13-13794

Peripheral neuropathy has been shown to exist in prediabetic and diabetic patients and animal models. However, the development of peripheral neuropathy in prediabetes and posthyperglycemia is likely different. The purpose of this study was to examine the progression of peripheral neuropathy in diet-induced obese rats and high-fat-fed rats treated with a low dose of streptozotocin, a model for type 2 diabetes, using standard endpoints as well as corneal sensitivity and innervation. Diet-induced obese rats and high-fat/low-dose streptozotocin diabetic rats were used to examine standard peripheral neuropathy endpoints and innervation of the cornea and corneal epithelium using corneal and standard confocal microscopy, respectively, and corneal sensitivity using a Cochet-Bonnet esthesiometer at three different time points. Obese rats and to a greater extent diabetic rats were insulin resistant. Obese and diabetic rats had developed sensory nerve deficits, but only diabetic rats had motor nerve dysfunction as determined by measuring nerve conduction velocity, thermal nociception, and intraepidermal nerve fiber density. In the cornea there was a decrease in corneal nerve fiber length, innervation of the corneal epithelium, and corneal sensitivity in both diet-induced obese and diabetic rats. These studies demonstrate that changes in corneal nerve innervation and sensitivity occur in both obese and type 2 diabetic rat models that are consistent with development of peripheral neuropathy. Examination of corneal nerve changes may be valuable endpoints for exploring potential treatments for peripheral neuropathy in both prediabetes with insulin resistance and diabetes.