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Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice

PURPOSE: Electroretinograms (ERGs) are abnormal in diabetic retinas before the appearance of vascular lesions, providing a possible biomarker for diabetic vision loss. Previously, we reported that decreased retinal dopamine (DA) levels in diabetic rodents contributed to early visual and retinal dysf...

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Autores principales: Kim, Moon K., Aung, Moe H., Mees, Lukas, Olson, Darin E., Pozdeyev, Nikita, Iuvone, P. Michael, Thule, Peter M., Pardue, Machelle T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788047/
https://www.ncbi.nlm.nih.gov/pubmed/29372256
http://dx.doi.org/10.1167/iovs.17-22692
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author Kim, Moon K.
Aung, Moe H.
Mees, Lukas
Olson, Darin E.
Pozdeyev, Nikita
Iuvone, P. Michael
Thule, Peter M.
Pardue, Machelle T.
author_facet Kim, Moon K.
Aung, Moe H.
Mees, Lukas
Olson, Darin E.
Pozdeyev, Nikita
Iuvone, P. Michael
Thule, Peter M.
Pardue, Machelle T.
author_sort Kim, Moon K.
collection PubMed
description PURPOSE: Electroretinograms (ERGs) are abnormal in diabetic retinas before the appearance of vascular lesions, providing a possible biomarker for diabetic vision loss. Previously, we reported that decreased retinal dopamine (DA) levels in diabetic rodents contributed to early visual and retinal dysfunction. In the current study, we examined whether oscillatory potentials (OPs) could serve as a potential marker for detecting early inner retinal dysfunction due to retinal DA deficiency. METHODS: Retinal function was tested with dark-adapted ERGs, taken at 3, 4, and 5 weeks after diabetes induction with streptozotocin. Electrical responses were analyzed and correlations were made with previously reported retinal DA levels. The effect of restoring systemic DA levels or removing DA from the retina in diabetic mice on OPs was assessed using L-3,4-dihydroxyphenylalanine (L-DOPA) treatments and retina-specific tyrosine hydroxylase (Th) knockout mice (rTHKO), respectively. RESULTS: Diabetic animals had significantly delayed OPs compared to control animals in response to dim, but not bright, flash stimuli. L-DOPA treatment preserved OP implicit time in diabetic mice. Diabetic rTHKO mice had further delayed OPs compared to diabetic mice with normal retinal Th, with L-DOPA treatment also providing benefit. Decreasing retinal DA levels significantly correlated with increasing OP delays mediated by rod pathways. CONCLUSIONS: Our data suggest that inner retinal dysfunction in early-stage diabetes is mediated by rod-pathway deficits and DA deficiencies. OP delays may be used to determine the earliest functional deficits in diabetic retinopathy and to establish an early treatment window for DA therapies that may prevent progressive vision loss.
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spelling pubmed-57880472018-01-30 Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice Kim, Moon K. Aung, Moe H. Mees, Lukas Olson, Darin E. Pozdeyev, Nikita Iuvone, P. Michael Thule, Peter M. Pardue, Machelle T. Invest Ophthalmol Vis Sci Visual Neuroscience PURPOSE: Electroretinograms (ERGs) are abnormal in diabetic retinas before the appearance of vascular lesions, providing a possible biomarker for diabetic vision loss. Previously, we reported that decreased retinal dopamine (DA) levels in diabetic rodents contributed to early visual and retinal dysfunction. In the current study, we examined whether oscillatory potentials (OPs) could serve as a potential marker for detecting early inner retinal dysfunction due to retinal DA deficiency. METHODS: Retinal function was tested with dark-adapted ERGs, taken at 3, 4, and 5 weeks after diabetes induction with streptozotocin. Electrical responses were analyzed and correlations were made with previously reported retinal DA levels. The effect of restoring systemic DA levels or removing DA from the retina in diabetic mice on OPs was assessed using L-3,4-dihydroxyphenylalanine (L-DOPA) treatments and retina-specific tyrosine hydroxylase (Th) knockout mice (rTHKO), respectively. RESULTS: Diabetic animals had significantly delayed OPs compared to control animals in response to dim, but not bright, flash stimuli. L-DOPA treatment preserved OP implicit time in diabetic mice. Diabetic rTHKO mice had further delayed OPs compared to diabetic mice with normal retinal Th, with L-DOPA treatment also providing benefit. Decreasing retinal DA levels significantly correlated with increasing OP delays mediated by rod pathways. CONCLUSIONS: Our data suggest that inner retinal dysfunction in early-stage diabetes is mediated by rod-pathway deficits and DA deficiencies. OP delays may be used to determine the earliest functional deficits in diabetic retinopathy and to establish an early treatment window for DA therapies that may prevent progressive vision loss. The Association for Research in Vision and Ophthalmology 2018-01 /pmc/articles/PMC5788047/ /pubmed/29372256 http://dx.doi.org/10.1167/iovs.17-22692 Text en Copyright 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Visual Neuroscience
Kim, Moon K.
Aung, Moe H.
Mees, Lukas
Olson, Darin E.
Pozdeyev, Nikita
Iuvone, P. Michael
Thule, Peter M.
Pardue, Machelle T.
Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice
title Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice
title_full Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice
title_fullStr Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice
title_full_unstemmed Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice
title_short Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in Diabetic Mice
title_sort dopamine deficiency mediates early rod-driven inner retinal dysfunction in diabetic mice
topic Visual Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788047/
https://www.ncbi.nlm.nih.gov/pubmed/29372256
http://dx.doi.org/10.1167/iovs.17-22692
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