Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy
| العنوان: | Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy |
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| المؤلفون: | Qianyi Zhang, Nuri Gueven, Lisa Foa, Krupali Shah, Jason A. Smith, Abraham Daniel, Dino Premilovac, Krystel L. Woolley, Zikai Feng, Nicole Bye |
| المصدر: | International Journal of Molecular Sciences, Vol 22, Iss 1016, p 1016 (2021) International Journal of Molecular Sciences Volume 22 Issue 3 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Visual acuity, genetic structures, Ubiquinone, Type 2 diabetes, medicine.disease_cause, Antioxidants, lcsh:Chemistry, 0302 clinical medicine, elamipretide, Idebenone, lcsh:QH301-705.5, Spectroscopy, General Medicine, Diabetic retinopathy, Computer Science Applications, mitochondria, medicine.anatomical_structure, Retinal ganglion cell, medicine.symptom, Oligopeptides, medicine.drug, medicine.medical_specialty, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, short-chain quinones, Ophthalmology, medicine, Animals, Rats, Long-Evans, Physical and Theoretical Chemistry, Molecular Biology, Retinal thinning, Vision, Ocular, diabetic-retinopathy, Diabetic Retinopathy, business.industry, Organic Chemistry, Elamipretide, medicine.disease, Rats, idebenone, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, 030221 ophthalmology & optometry, business, Oxidative stress |
| الوصف: | 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&ndash 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&ndash 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8370530d9fe1551d2f083f4bcf5b1e44 https://www.mdpi.com/1422-0067/22/3/1016 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8370530d9fe1551d2f083f4bcf5b1e44 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16616596 14220067 |
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