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Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy

Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunctio...

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Autores principales: Daniel, Abraham, Premilovac, Dino, Foa, Lisa, Feng, Zikai, Shah, Krupali, Zhang, Qianyi, Woolley, Krystel L., Bye, Nicole, Smith, Jason A., Gueven, Nuri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864174/
https://www.ncbi.nlm.nih.gov/pubmed/33498409
http://dx.doi.org/10.3390/ijms22031016
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author Daniel, Abraham
Premilovac, Dino
Foa, Lisa
Feng, Zikai
Shah, Krupali
Zhang, Qianyi
Woolley, Krystel L.
Bye, Nicole
Smith, Jason A.
Gueven, Nuri
author_facet Daniel, Abraham
Premilovac, Dino
Foa, Lisa
Feng, Zikai
Shah, Krupali
Zhang, Qianyi
Woolley, Krystel L.
Bye, Nicole
Smith, Jason A.
Gueven, Nuri
author_sort Daniel, Abraham
collection PubMed
description Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR. Consequently, drug candidates that aim at normalizing mitochondrial function could be an attractive therapeutic approach. This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR. The model effectively mimicked type 2 diabetes over 21 weeks. During this period, visual acuity was monitored by measuring optokinetic response (OKR). Vision loss occurred 5–8 weeks after the onset of hyperglycemia. After 10 weeks of hyperglycemia, visual function was reduced by 65%. From this point, the right eyes of the animals were topically treated once daily with the test compounds. The left, untreated eye served as an internal control. Only three weeks of topical treatment significantly restored vision from 35% to 58–80%, while visual acuity of the non-treated eyes continued to deteriorate. Interestingly, the two novel SCQs restored visual acuity better than idebenone or elamipretide. This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR.
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spelling pubmed-78641742021-02-06 Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy Daniel, Abraham Premilovac, Dino Foa, Lisa Feng, Zikai Shah, Krupali Zhang, Qianyi Woolley, Krystel L. Bye, Nicole Smith, Jason A. Gueven, Nuri Int J Mol Sci Article Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR. Consequently, drug candidates that aim at normalizing mitochondrial function could be an attractive therapeutic approach. This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR. The model effectively mimicked type 2 diabetes over 21 weeks. During this period, visual acuity was monitored by measuring optokinetic response (OKR). Vision loss occurred 5–8 weeks after the onset of hyperglycemia. After 10 weeks of hyperglycemia, visual function was reduced by 65%. From this point, the right eyes of the animals were topically treated once daily with the test compounds. The left, untreated eye served as an internal control. Only three weeks of topical treatment significantly restored vision from 35% to 58–80%, while visual acuity of the non-treated eyes continued to deteriorate. Interestingly, the two novel SCQs restored visual acuity better than idebenone or elamipretide. This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR. MDPI 2021-01-20 /pmc/articles/PMC7864174/ /pubmed/33498409 http://dx.doi.org/10.3390/ijms22031016 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Daniel, Abraham
Premilovac, Dino
Foa, Lisa
Feng, Zikai
Shah, Krupali
Zhang, Qianyi
Woolley, Krystel L.
Bye, Nicole
Smith, Jason A.
Gueven, Nuri
Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy
title Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy
title_full Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy
title_fullStr Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy
title_full_unstemmed Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy
title_short Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy
title_sort novel short-chain quinones to treat vision loss in a rat model of diabetic retinopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864174/
https://www.ncbi.nlm.nih.gov/pubmed/33498409
http://dx.doi.org/10.3390/ijms22031016
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