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Novel short-chain quinones to treat vision loss in a rat model of diabetic retinopathy

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Daniel, A, Premilovac, D ORCID: 0000-0003-2770-4713, Foa, L ORCID: 0000-0003-4131-8341, Feng, ZK, Shah, K, Zhang, Q, Woolley, KL, Bye, N ORCID: 0000-0003-0976-5870, Smith, Jason Alfred ORCID: 0000-0001-6313-3298 and Gueven, N ORCID: 0000-0003-3782-767X 2021 , 'Novel short-chain quinones to treat vision loss in a rat model of diabetic retinopathy' , International Journal of Molecular Sciences, vol. 22, no. 3 , doi: 10.3390/ijms22031016.

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Abstract

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.

Item Type: Article
Authors/Creators:Daniel, A and Premilovac, D and Foa, L and Feng, ZK and Shah, K and Zhang, Q and Woolley, KL and Bye, N and Smith, Jason Alfred and Gueven, N
Keywords: diabetic retinopathy, short chain quinones, idebenone, mitochondria, elamipretide, diabetic-retinopathy,
Journal or Publication Title: International Journal of Molecular Sciences
Publisher: 33498409
ISSN: 1422-0067
DOI / ID Number: 10.3390/ijms22031016
Copyright Information:

Copyright: © 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 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).

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