Progressive Loss of Corneal Nerve Fibers and Sensitivity in Rats Modeling Obesity and Type 2 Diabetes Is Reversible with Omega-3 Fatty Acid Intervention: Supporting Cornea Analyses as a Marker for Peripheral Neuropathy and Treatment

• Main Authors: Coppey L, Davidson E, Shevalye H, Obrosov A, Torres M, Yorek MA
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-04-01
• Series: Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
• Subjects: corneal nerves; peripheral neuropathy; omega-3 polyunsaturated fatty acids; diabetes; obesity
• Online Access: https://www.dovepress.com/progressive-loss-of-corneal-nerve-fibers-and-sensitivity-in-rats-model-peer-reviewed-article-DMSO

Lawrence Coppey,1 Eric Davidson,1 Hanna Shevalye,1 Alexander Obrosov,1 Michael Torres,1 Mark A Yorek1– 4 1Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; 2Department of Veterans Affairs, Iowa City Health Care System, Iowa City, IA, USA; 3Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, USA; 4Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USACorrespondence: Mark A YorekDepartment of Veterans Affairs, Iowa City Health Care System, Iowa City, IA 52246 Tel [phone] ext. 7696Fax [phone]Email [e-mail]: To determine whether cornea nerve fiber density and/or corneal function are valid markers for early detection and treatment of peripheral neuropathy in rats modeling prediabetes and type 2 diabetes.Methods: High-fat feeding combined without or with low-dose streptozotocin was used to create rat models for prediabetes and type 2 diabetes that were 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. There were three time points examined in each of the three conditions with 12 rats per group. The latest time point (24 weeks of high-fat diet with or without 16 weeks of hyperglycemia) was used to examine reversibility of neuro and vascular pathology following 16 weeks of treatment with menhaden oil, a natural source of long-chain omega-3 polyunsaturated fatty acids. The number of rats in the intervention study ranged from 6 to  17.Results: 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 pre-diabetic 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 significantly reversed both vascular and peripheral nerve damage induced by chronic obesity or type 2 diabetes.Conclusion: These studies provide support for examination of corneal structure and function as an early marker of peripheral neuropathy in prediabetes and type 2 diabetes. Furthermore, we demonstrate that omega-3 polyunsaturated fatty acids derived from fish oil are an effective treatment for peripheral neuropathy that occurs with chronic obesity or type 2 diabetes.Keywords: corneal nerves, peripheral neuropathy, omega-3 polyunsaturated fatty acids, diabetes, obesity