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...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
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 |
id |
doaj-3fc4afcfd1274ed4812809a71632c6fc |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
work_keys_str_mv |
AT dmitryvchistyakov mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT viktoriiaebaksheeva mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT veronikavtiulina mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT sergeivgoriainov mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT nadezhdavazbukina mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT olgasgancharova mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT eugeneaarifulin mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT sergeyvkomarov mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT viktorvchistyakov mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT nataliaktikhomirova mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT andreyazamyatnin mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT pavelpphilippov mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT ivanisenin mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT marinagsergeeva mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor AT evgeniyuzernii mechanismsandtreatmentoflightinducedretinaldegenerationassociatedinflammationinsightsfrombiochemicalprofilingoftheaqueoushumor |
_version_ |
1724882309351473152 |
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 |