142809-Novel short-chain quinones to treat vision loss in a rat model of diabetic retinopathy.pdf (3.62 MB)
Novel short-chain quinones to treat vision loss in a rat model of diabetic retinopathy
journal contribution
posted on 2023-05-20, 20:59 authored by Daniel, A, Dino PremilovacDino Premilovac, Lisa FoaLisa Foa, Feng, ZK, Shah, K, Zhang, Q, Krystel WoolleyKrystel Woolley, Nicole ByeNicole Bye, Jason SmithJason Smith, Nuri GuvenNuri GuvenDiabetic 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.
History
Publication title
International Journal of Molecular SciencesVolume
22Article number
1016Number
1016Pagination
1-17ISSN
1422-0067Department/School
School of Health SciencesPublisher
33498409Place of publication
Matthaeusstrasse 11, Basel, Switzerland, Ch-4057Rights statement
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/).Repository Status
- Open