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

Lawrence Coppey; Eric Davidson; Hanna Shevalye; Alexander Obrosov; Michael Torres; Mark A Yorek

doi:10.2147/DMSO.S247571

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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

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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

Lawrence Coppey, Eric Davidson, Hanna Shevalye, Alexander Obrosov, Michael Torres and Mark A Yorek

Diabetes, metabolic syndrome and obesity, Vol.13, pp.1367-1384

2020

DOI: 10.2147/DMSO.S247571

PMCID: PMC7189026

PMID: 32425569

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Abstract

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. 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. 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. 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.

corneal nerves

diabetes

peripheral neuropathy

obesity

omega-3 polyunsaturated fatty acids

Details

Title: Subtitle: 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
Creators: Lawrence Coppey - University of Iowa
Eric Davidson - University of Iowa
Hanna Shevalye - University of Iowa
Alexander Obrosov - University of Iowa
Michael Torres - University of Iowa
Mark A Yorek - University of Iowa
Resource Type: Journal article
Publication Details: Diabetes, metabolic syndrome and obesity, Vol.13, pp.1367-1384
DOI: 10.2147/DMSO.S247571
PMID: 32425569
PMCID: PMC7189026
NLM abbreviation: Diabetes Metab Syndr Obes
ISSN: 1178-7007
eISSN: 1178-7007
Grant note: R01 DK107399 / NIDDK NIH HHS I01 RX000889 / RRD VA
Language: English
Date published: 2020
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984359893402771

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