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 we...

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Main Authors: Dmitry V. Chistyakov, Viktoriia E. Baksheeva, Veronika V. Tiulina, Sergei V. Goriainov, Nadezhda V. Azbukina, Olga S. Gancharova, Eugene A. Arifulin, Sergey V. Komarov, Viktor V. Chistyakov, Natalia K. Tikhomirova, Andrey A. Zamyatnin, Pavel P. Philippov, Ivan I. Senin, Marina G. Sergeeva, Evgeni Yu. Zernii
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/3/704
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author Dmitry V. Chistyakov
Viktoriia E. Baksheeva
Veronika V. Tiulina
Sergei V. Goriainov
Nadezhda V. Azbukina
Olga S. Gancharova
Eugene A. Arifulin
Sergey V. Komarov
Viktor V. Chistyakov
Natalia K. Tikhomirova
Andrey A. Zamyatnin
Pavel P. Philippov
Ivan I. Senin
Marina G. Sergeeva
Evgeni Yu. Zernii
spellingShingle Dmitry V. Chistyakov
Viktoriia E. Baksheeva
Veronika V. Tiulina
Sergei V. Goriainov
Nadezhda V. Azbukina
Olga S. Gancharova
Eugene A. Arifulin
Sergey V. Komarov
Viktor V. Chistyakov
Natalia K. Tikhomirova
Andrey A. Zamyatnin
Pavel P. Philippov
Ivan I. Senin
Marina G. Sergeeva
Evgeni Yu. Zernii
Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor
International Journal of Molecular Sciences
ocular inflammation
light-induced retinal damage
age-related macular degeneration
oxidative stress
polyunsaturated fatty acids
oxylipins
mitochondria-targeted antioxidant
skq1
non-steroidal anti-inflammatory drugs
nepafenac
author_facet Dmitry V. Chistyakov
Viktoriia E. Baksheeva
Veronika V. Tiulina
Sergei V. Goriainov
Nadezhda V. Azbukina
Olga S. Gancharova
Eugene A. Arifulin
Sergey V. Komarov
Viktor V. Chistyakov
Natalia K. Tikhomirova
Andrey A. Zamyatnin
Pavel P. Philippov
Ivan I. Senin
Marina G. Sergeeva
Evgeni Yu. Zernii
author_sort Dmitry V. Chistyakov
title Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor
title_short Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor
title_full Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor
title_fullStr Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor
title_full_unstemmed Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor
title_sort mechanisms and treatment of light-induced retinal degeneration-associated inflammation: insights from biochemical profiling of the aqueous humor
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2020-01-01
description 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.
topic ocular inflammation
light-induced retinal damage
age-related macular degeneration
oxidative stress
polyunsaturated fatty acids
oxylipins
mitochondria-targeted antioxidant
skq1
non-steroidal anti-inflammatory drugs
nepafenac
url https://www.mdpi.com/1422-0067/21/3/704
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spelling doaj-3fc4afcfd1274ed4812809a71632c6fc2020-11-25T02:18:25ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-01-0121370410.3390/ijms21030704ijms21030704Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous HumorDmitry V. Chistyakov0Viktoriia E. Baksheeva1Veronika V. Tiulina2Sergei V. Goriainov3Nadezhda V. Azbukina4Olga S. Gancharova5Eugene A. Arifulin6Sergey V. Komarov7Viktor V. Chistyakov8Natalia K. Tikhomirova9Andrey A. Zamyatnin10Pavel P. Philippov11Ivan I. Senin12Marina G. Sergeeva13Evgeni Yu. Zernii14Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaSREC PFUR Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow RussiaFaculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, 119234 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaSkryabin Moscow State Academy of Veterinary Medicine and Biotechnology, 109472 Moscow, RussiaSREC PFUR Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaOcular 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.https://www.mdpi.com/1422-0067/21/3/704ocular inflammationlight-induced retinal damageage-related macular degenerationoxidative stresspolyunsaturated fatty acidsoxylipinsmitochondria-targeted antioxidantskq1non-steroidal anti-inflammatory drugsnepafenac