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Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy

Proliferative diabetic retinopathy (PDR), neovascular age-related macular degeneration (nvAMD), retinopathy of prematurity (ROP) and other eye diseases are characterized by retinal and/or choroidal neovascularization, ultimately causing vision loss in millions of people worldwide. nvAMD and PDR are...

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Autores principales: Hartman, Gabriella D., Lambert-Cheatham, Nathan A., Kelley, Mark R., Corson, Timothy W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508814/
https://www.ncbi.nlm.nih.gov/pubmed/34638620
http://dx.doi.org/10.3390/ijms221910279
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author Hartman, Gabriella D.
Lambert-Cheatham, Nathan A.
Kelley, Mark R.
Corson, Timothy W.
author_facet Hartman, Gabriella D.
Lambert-Cheatham, Nathan A.
Kelley, Mark R.
Corson, Timothy W.
author_sort Hartman, Gabriella D.
collection PubMed
description Proliferative diabetic retinopathy (PDR), neovascular age-related macular degeneration (nvAMD), retinopathy of prematurity (ROP) and other eye diseases are characterized by retinal and/or choroidal neovascularization, ultimately causing vision loss in millions of people worldwide. nvAMD and PDR are associated with aging and the number of those affected is expected to increase as the global median age and life expectancy continue to rise. With this increase in prevalence, the development of novel, orally bioavailable therapies for neovascular eye diseases that target multiple pathways is critical, since current anti-vascular endothelial growth factor (VEGF) treatments, delivered by intravitreal injection, are accompanied with tachyphylaxis, a high treatment burden and risk of complications. One potential target is apurinic/apyrimidinic endonuclease 1/reduction-oxidation factor 1 (APE1/Ref-1). The multifunctional protein APE1/Ref-1 may be targeted via inhibitors of its redox-regulating transcription factor activation activity to modulate angiogenesis, inflammation, oxidative stress response and cell cycle in neovascular eye disease; these inhibitors also have neuroprotective effects in other tissues. An APE1/Ref-1 small molecule inhibitor is already in clinical trials for cancer, PDR and diabetic macular edema. Efforts to develop further inhibitors are underway. APE1/Ref-1 is a novel candidate for therapeutically targeting neovascular eye diseases and alleviating the burden associated with anti-VEGF intravitreal injections.
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spelling pubmed-85088142021-10-13 Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy Hartman, Gabriella D. Lambert-Cheatham, Nathan A. Kelley, Mark R. Corson, Timothy W. Int J Mol Sci Review Proliferative diabetic retinopathy (PDR), neovascular age-related macular degeneration (nvAMD), retinopathy of prematurity (ROP) and other eye diseases are characterized by retinal and/or choroidal neovascularization, ultimately causing vision loss in millions of people worldwide. nvAMD and PDR are associated with aging and the number of those affected is expected to increase as the global median age and life expectancy continue to rise. With this increase in prevalence, the development of novel, orally bioavailable therapies for neovascular eye diseases that target multiple pathways is critical, since current anti-vascular endothelial growth factor (VEGF) treatments, delivered by intravitreal injection, are accompanied with tachyphylaxis, a high treatment burden and risk of complications. One potential target is apurinic/apyrimidinic endonuclease 1/reduction-oxidation factor 1 (APE1/Ref-1). The multifunctional protein APE1/Ref-1 may be targeted via inhibitors of its redox-regulating transcription factor activation activity to modulate angiogenesis, inflammation, oxidative stress response and cell cycle in neovascular eye disease; these inhibitors also have neuroprotective effects in other tissues. An APE1/Ref-1 small molecule inhibitor is already in clinical trials for cancer, PDR and diabetic macular edema. Efforts to develop further inhibitors are underway. APE1/Ref-1 is a novel candidate for therapeutically targeting neovascular eye diseases and alleviating the burden associated with anti-VEGF intravitreal injections. MDPI 2021-09-24 /pmc/articles/PMC8508814/ /pubmed/34638620 http://dx.doi.org/10.3390/ijms221910279 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hartman, Gabriella D.
Lambert-Cheatham, Nathan A.
Kelley, Mark R.
Corson, Timothy W.
Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy
title Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy
title_full Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy
title_fullStr Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy
title_full_unstemmed Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy
title_short Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy
title_sort inhibition of ape1/ref-1 for neovascular eye diseases: from biology to therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508814/
https://www.ncbi.nlm.nih.gov/pubmed/34638620
http://dx.doi.org/10.3390/ijms221910279
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