Corneal Sensitivity to Hyperosmolar Eye Drops: A Novel Behavioral Assay to Assess Diabetic Peripheral Neuropathy

Matthew S Yorek; Eric P Davidson; Pieter Poolman; Lawrence J Coppey; Alexander Obrosov; Amey Holmes; Randy H Kardon; Mark A Yorek

doi:10.1167/iovs.16-19435

Back

Corneal Sensitivity to Hyperosmolar Eye Drops: A Novel Behavioral Assay to Assess Diabetic Peripheral Neuropathy

Journal article

Open access

Peer reviewed

Corneal Sensitivity to Hyperosmolar Eye Drops: A Novel Behavioral Assay to Assess Diabetic Peripheral Neuropathy

Matthew S Yorek, Eric P Davidson, Pieter Poolman, Lawrence J Coppey, Alexander Obrosov, Amey Holmes, Randy H Kardon and Mark A Yorek

Investigative ophthalmology & visual science, Vol.57(6), pp.2412-2419

05/01/2016

DOI: 10.1167/iovs.16-19435

PMCID: PMC5113984

PMID: 27145474

Files and links (1)

url

https://doi.org/10.1167/iovs.16-19435View

Published (Version of record) Open Access

Abstract

Diagnosis of peripheral neuropathy (PN), which affects approximately 50% of the diabetic population, is subjective, with many patients seeking a diagnosis only after presenting with symptoms. Recently, in vivo confocal microscopy of subepithelial corneal nerve density has been promoted as a surrogate marker for early detection of PN, but imaging of corneal nerves requires sophisticated instrumentation, expertise in confocal imaging, cooperative patients, and automated analysis tools to derive corneal nerve density. As an alternative, we developed a simple screening method that is based on the sensitivity of corneal nerves to cause reflex eyelid squinting in response to hyperosmolar eye drops. Eyes of control and type 2 diabetic rats were given an eye drop of a 290- to 900-mOsm solution, and the ocular response was video recorded. Other neuropathic end points including nerve conduction velocity and subepithelial cornea nerve density were determined. Motor and sensory nerve conduction velocity and total nerve fiber length of corneal nerves in the subepithelial layer were significantly decreased in diabetic rats. Applying the hyperosmotic solutions to the ocular surface caused an osmolarity-dependent increase in squinting of the treated eye in control rats. Squinting was almost totally blocked by preapplication of proparacaine or N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide, a transient receptor potential melastatin-8 channel blocker. Squinting in response to the 900-mOsm solution was significantly reduced in diabetic rats. Preclinical studies show that evaluation of corneal sensitivity may be an alternative method for the early detection of PN and has potential for translation to clinical studies.

Ophthalmic Solutions - administration & dosage

Nociception - physiology

Rats

Male

Nerve Fibers - drug effects

Rats, Sprague-Dawley

Behavior, Animal

Microscopy, Confocal

Animals

Cornea - drug effects

Osmolar Concentration

Diabetes Mellitus, Experimental

Cornea - innervation

Diabetic Neuropathies - diagnosis

Saline Solution, Hypertonic - administration & dosage

Early Diagnosis

Diabetic Neuropathies - physiopathology

Details

Title: Subtitle: Corneal Sensitivity to Hyperosmolar Eye Drops: A Novel Behavioral Assay to Assess Diabetic Peripheral Neuropathy
Creators: Matthew S Yorek - University of Iowa
Eric P Davidson - Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Pieter Poolman - University of Iowa
Lawrence J Coppey - Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Alexander Obrosov - Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Amey Holmes - Department of Veterans Affairs Iowa City Health Care System, Iowa City, Iowa, United States
Randy H Kardon - University of Iowa
Mark A Yorek - University of Iowa
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.57(6), pp.2412-2419
DOI: 10.1167/iovs.16-19435
PMID: 27145474
PMCID: PMC5113984
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 DK107399 / NIDDK NIH HHS I01 RX000889 / RRD VA
Language: English
Date published: 05/01/2016
Academic Unit: Iowa Neuroscience Institute; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983979994402771

Metrics

32 Record Views

18 Times Cited - Web of Science