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

Autor: Qianyi Zhang, Nuri Gueven, Lisa Foa, Krupali Shah, Jason A. Smith, Abraham Daniel, Dino Premilovac, Krystel L. Woolley, Zikai Feng, Nicole Bye
Jazyk: angličtina
Rok vydání: 2021
Předmět:
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
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 1016, p 1016 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 3
ISSN: 1661-6596
1422-0067
Popis: 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.
Databáze: OpenAIRE
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