124-OR: Progressive Loss of Corneal Nerve Fibers and Sensitivity with Duration of Obesity Type 2 Diabetes in Sprague-Dawley Rats: Valid Marker for Peripheral Neuropathy and Treatment

Abstract

Purpose: Determine whether density of nerve fibers in the cornea and corneal function are valid markers for early detection and treatment of peripheral neuropathy in rat models of prediabetes and type 2 diabetes. Methods: Rat models for prediabetes and type 2 diabetes were created and longitudinally studied for loss of structure and function of sensory nerves in the cornea and skin as well as nerve conduction velocity and vascular reactivity of epineurial arterioles. Reversibility of neuro and vascular pathology was also examined in these models following chronic obesity or type 2 diabetes after dietary intervention with menhaden oil a natural source of long chain omega-3 polyunsaturated fatty acids. Results and Conclusions: Our longitudinal study demonstrated that vascular and neural dysfunction associated with obesity or type 2 diabetes occur early and are progressive. Decrease in cornea nerve fiber length and function were valid markers of disease in both the prediabetic and diabetic rat models and were more sensitive than decrease in intraepidermal nerve fiber density of the skin and thermal nociception of the hindpaw. Late intervention with menhaden oil reversed both vascular and peripheral damage induced by chronic obesity or type 2 diabetes. These studies provide support for examination of corneal structure and function as an early marker of peripheral neuropathy in prediabetes and diabetes. Furthermore, we demonstrate that omega-3 polyunsaturated fatty acids derived from fish oil as an effective treatment for peripheral neuropathy that occurs with chronic obesity or type 2 diabetes. Disclosure M.A. Yorek: Consultant; Self; Novo Nordisk Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK107339); U.S. Department of Veterans Affairs (RX000889)