Rodent Hyperglycemia-Induced Inner Retinal Deficits are Mirrored in Human Diabetes

• Type of Material: Article
• Authors: Machelle Pardue, Emory University; Claire S. Barnes, Emory University; Moon K. Kim, Emory University; Moe H. Aung, Emory University; Raj Amarnath, Veterans Affairs Medical Center; Darin Olson, Emory University; Peter Martin Thule, Emory University
• Language: English
• Date: 2014-05
• Publisher: Association for Research in Vision and Ophthalmology (ARVO)
• Publication Version: Final Published Version
• Copyright Statement: © ARVO
• Final Published Version (URL): http://tvstjournal.org/doi/abs/10.1167/tvst.3.3.6
• Title of Journal or Parent Work: Translational Vision Science & Technology
• ISSN: 2164-2591
• Volume: 3
• Issue: 3
• Start Page: 6
• End Page: 6
• Grant/Funding Information: Supported by a Pilot grant from Atlanta VA Rehabilitation Research & Development Center of Excellence, Rehabilitation Research and Development Service (Merit Award E0951-R [MP], Research Career Scientist Award [MP], Career Development Award C4758W [CB]) and Biological Laboratory Research and Development Service (Merit Award [PMT]) of the Department of Veterans Affairs, Juvenile Diabetes Research Foundation Innovative Award (PMT), Research to Prevent Blindness (Department of Ophthalmology, Emory University), and National Institutes of Health P30 EY006360.
• Keywords: diabetic retinopathy; electroretinography; rod vision
• Research Categories: Health Sciences, Opthamology; Biology, Neuroscience; Health Sciences, General

Abstract

Purpose To evaluate the utility of low luminance stimuli to functionally probe inner retinal rod pathways in the context of diabetes mellitus in both rat and human subjects. Methods Inner retinal dysfunction was assessed using oscillatory potential (OP) delays in diabetic rats. Scotopic electroretinograms (ERGs) in response to a series of increasing flash luminances were recorded from streptozotocin (STZ)-treated and control Sprague-Dawley rats after 7, 14, 20, and 29 weeks of hyperglycemia. We then evaluated OP delays in human diabetic subjects with (DR) and without (DM) diabetic retinopathy using the International Society for Clinical Electrophysiology in Vision (ISCEV) standard scotopic protocol and two additional dim test flashes. Results Beginning 7 weeks after STZ, OP implicit times in diabetic rats were progressively delayed in response to dim, but not bright stimuli. In many diabetic subjects the standard ISCEV dim flash failed to illicit measureable OPs. However, OPs became measurable using a brighter, nonstandard dim flash (Test Flash 1, −1.43 log cd s/m2), and exhibited prolonged implicit times in the DM group compared with control subjects (CTRL). Conclusions Delays in scotopic OP implicit times are an early response to hyperglycemia in diabetic rats. A similar, inner retinal, rod-driven response was detected in diabetic human subjects without diabetic retinopathy, only when a nonstandard ISCEV flash intensity was employed during ERG testing. Translational Relevance The addition of a dim stimulus to standard ISCEV flashes with assessment of OP latency during ERG testing may provide a detection method for early retinal dysfunction in diabetic patients.