Novel Detection and Restorative Levodopa Treatment for Preclinical Diabetic Retinopathy
- 12 February 2020
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 69 (7), 1518-1527
- https://doi.org/10.2337/db19-0869
Abstract
Diabetic retinopathy (DR) is diagnosed clinically by directly viewing retinal vascular changes during ophthalmoscopy or through fundus photographs. However, electroretinography (ERG) studies in humans and rodents have revealed that retinal dysfunction is demonstrable prior to the development of visible vascular defects. Specifically, delays in dark-adapted ERG oscillatory potential (OP) implicit times in response to dim-flash stimuli (<−1.8 log cd · s/m2) occur prior to clinically recognized DR. Animal studies suggest that retinal dopamine deficiency underlies these early functional deficits. In this study, we randomized individuals with diabetes, without clinically detectable retinopathy, to treatment with either low- or high-dose Sinemet (levodopa plus carbidopa) for 2 weeks and compared their ERG findings with those of control subjects (no diabetes). We assessed dim-flash–stimulated OP delays using a novel handheld ERG system (RETeval) at baseline and 2 and 4 weeks. RETeval recordings identified significant OP implicit time delays in individuals with diabetes without retinopathy compared with age-matched control subjects (P < 0.001). After 2 weeks of Sinemet treatment, OP implicit times were restored to control values, and these improvements persisted even after a 2-week washout. We conclude that detection of dim-flash OP delays could provide early detection of DR and that Sinemet treatment may reverse retinal dysfunction.Keywords
Funding Information
- U.S. Department of Veterans Affairs (RX002928, RX002342, IK6-RX003134)
- Center for Scientific Review (P30-EY-006360)
- Research to Prevent Blindness
- U.S. Department of Veterans Affairs (I01-RX2615)
This publication has 54 references indexed in Scilit:
- Intrarenal Dopamine Inhibits Progression of Diabetic NephropathyDiabetes, 2012
- Retinal Dopamine Mediates Multiple Dimensions of Light-Adapted VisionJournal of Neuroscience, 2012
- Spatial frequency threshold and contrast sensitivity of an optomotor behavior are impaired in the Ins2Akita mouse model of diabetesBehavioural Brain Research, 2012
- Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetesDiabetologia, 2010
- ISCEV Standard for full-field clinical electroretinography (2008 update)Documenta Ophthalmologica, 2008
- Early Inner Retinal Dysfunction in Streptozotocin-Induced Diabetic RatsInvestigative Ophthalmology & Visual Science, 2008
- Early electroretinographic features of streptozotocin‐induced diabetic retinopathyClinical & Experimental Ophthalmology, 2007
- Oxidative Stress and Diabetic RetinopathyExperimental Diabetes Research, 2007
- Loss of Cholinergic and Dopaminergic Amacrine Cells in Streptozotocin-Diabetic Rat and Ins2Akita-Diabetic Mouse RetinasInvestigative Ophthalmology & Visual Science, 2006
- A randomized crossover trial of levodopa in congestive heart failureJournal of Cardiac Failure, 1996