Mechanisms and treatment of light-induced retinal degeneration-associated inflammation: Insights from biochemical profiling of the aqueous humor

Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Authors
Chistyakov D.V. 1 , Baksheeva V.E.1 , Tiulina V.V.1, 2 , Goriainov S.V. 3 , Azbukina N.V.4 , Gancharova O.S.1, 4 , Arifulin E.A. 1 , Komarov S.V.2 , Chistyakov V.V. 3 , Tikhomirova N.K.1 , Zamyatnin A.A.Jr. , Philippov P.P.1 , Senin I.I.1 , Sergeeva M.G. 1 , Zernii E.Y.1, 5
Publisher
MDPI AG
Number of issue
3
Language
English
Status
Published
Number
704
Volume
21
Year
2020
Organizations
  • 1 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russian Federation
  • 2 Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, 109472, Russian Federation
  • 3 SREC PFUR Peoples’ Friendship University of Russia (RUDN University), Moscow, 117198, Russian Federation
  • 4 Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, Moscow, 119234, Russian Federation
  • 5 Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russian Federation
Keywords
Age-related macular degeneration; Light-induced retinal damage; Mitochondria-targeted antioxidant; Nepafenac; Non-steroidal anti-inflammatory drugs; Ocular inflammation; Oxidative stress; Oxylipins; Polyunsaturated fatty acids; SkQ1
Date of creation
10.02.2020
Date of change
10.02.2020
Short link
https://repository.rudn.ru/en/records/article/record/56524/
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