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All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion
PURPOSE: Extracellular accumulation of all-trans-retinaldehyde (atRAL), a highly reactive visual cycle intermediate, is toxic to cells of the outer retina and contributes to retinal and macular degenerations. However, the contribution of atRAL to retinal capillary function has not been studied. We h...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415894/ https://www.ncbi.nlm.nih.gov/pubmed/32492112 http://dx.doi.org/10.1167/iovs.61.6.8 |
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author | Dreffs, Alyssa Lin, Cheng-Mao Liu, Xuwen Shanmugam, Sumathi Abcouwer, Steven F. Kern, Timothy S. Antonetti, David A. |
author_facet | Dreffs, Alyssa Lin, Cheng-Mao Liu, Xuwen Shanmugam, Sumathi Abcouwer, Steven F. Kern, Timothy S. Antonetti, David A. |
author_sort | Dreffs, Alyssa |
collection | PubMed |
description | PURPOSE: Extracellular accumulation of all-trans-retinaldehyde (atRAL), a highly reactive visual cycle intermediate, is toxic to cells of the outer retina and contributes to retinal and macular degenerations. However, the contribution of atRAL to retinal capillary function has not been studied. We hypothesized that atRAL released from the outer retina can contribute to retinal vascular permeability. We, therefore, tested the contribution of atRAL to retinal ischemia-reperfusion (IR)-induced vascular permeability. METHODS: IR was induced in mice by transient increase in intraocular pressure followed by natural reperfusion. The visual cycle was ablated in the Lrat(−)(/)(−) mice, reduced by dark adaptation or the use of the RPE65 inhibitor and atRAL scavenger emixustat. Accumulation of FITC-BSA was used to assess vascular permeability and DNA fragmentation quantified cell death after IR. Primary bovine retinal endothelial cell (BREC) culture was used to measure the direct effects of atRAL on endothelial permeability and cell death. RESULTS: Inhibition of the visual cycle by Lrat(−)(/)(−), dark adaptation, or with emixustat, all reduced approximately half of IR induced vascular permeability at 48 hours. An increase in BREC permeability with atRAL coincided with lactate dehydrogenase (LDH) release, a measure of cell death. Both permeability and toxicity were blocked by emixustat. CONCLUSIONS: Outer retinal pathology may contribute to vascular permeability by release of atRAL, which can act directly on vascular endothelial cells to alter barrier properties and induce cell death. These studies may have implications for a variety of blinding eye diseases that include outer retinal damage and retinal vascular permeability. |
format | Online Article Text |
id | pubmed-7415894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-74158942020-08-24 All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion Dreffs, Alyssa Lin, Cheng-Mao Liu, Xuwen Shanmugam, Sumathi Abcouwer, Steven F. Kern, Timothy S. Antonetti, David A. Invest Ophthalmol Vis Sci Retina PURPOSE: Extracellular accumulation of all-trans-retinaldehyde (atRAL), a highly reactive visual cycle intermediate, is toxic to cells of the outer retina and contributes to retinal and macular degenerations. However, the contribution of atRAL to retinal capillary function has not been studied. We hypothesized that atRAL released from the outer retina can contribute to retinal vascular permeability. We, therefore, tested the contribution of atRAL to retinal ischemia-reperfusion (IR)-induced vascular permeability. METHODS: IR was induced in mice by transient increase in intraocular pressure followed by natural reperfusion. The visual cycle was ablated in the Lrat(−)(/)(−) mice, reduced by dark adaptation or the use of the RPE65 inhibitor and atRAL scavenger emixustat. Accumulation of FITC-BSA was used to assess vascular permeability and DNA fragmentation quantified cell death after IR. Primary bovine retinal endothelial cell (BREC) culture was used to measure the direct effects of atRAL on endothelial permeability and cell death. RESULTS: Inhibition of the visual cycle by Lrat(−)(/)(−), dark adaptation, or with emixustat, all reduced approximately half of IR induced vascular permeability at 48 hours. An increase in BREC permeability with atRAL coincided with lactate dehydrogenase (LDH) release, a measure of cell death. Both permeability and toxicity were blocked by emixustat. CONCLUSIONS: Outer retinal pathology may contribute to vascular permeability by release of atRAL, which can act directly on vascular endothelial cells to alter barrier properties and induce cell death. These studies may have implications for a variety of blinding eye diseases that include outer retinal damage and retinal vascular permeability. The Association for Research in Vision and Ophthalmology 2020-06-03 /pmc/articles/PMC7415894/ /pubmed/32492112 http://dx.doi.org/10.1167/iovs.61.6.8 Text en Copyright 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Retina Dreffs, Alyssa Lin, Cheng-Mao Liu, Xuwen Shanmugam, Sumathi Abcouwer, Steven F. Kern, Timothy S. Antonetti, David A. All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion |
title | All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion |
title_full | All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion |
title_fullStr | All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion |
title_full_unstemmed | All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion |
title_short | All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion |
title_sort | all-trans-retinaldehyde contributes to retinal vascular permeability in ischemia reperfusion |
topic | Retina |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415894/ https://www.ncbi.nlm.nih.gov/pubmed/32492112 http://dx.doi.org/10.1167/iovs.61.6.8 |
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