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End binding-3 inhibitor activates regenerative program in age-related macular degeneration

Wet age-related macular degeneration (AMD), characterized by leaky neovessels emanating from the choroid, is a main cause of blindness. As current treatments for wet AMD require regular intravitreal injections of anti-vascular endothelial growth factor (VEGF) biologics, there is a need for the devel...

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Autores principales: Lee, Quinn, Chan, Wan Ching, Qu, Xinyan, Sun, Ying, Abdelkarim, Hazem, Le, Jonathan, Saqib, Uzma, Sun, Mitchell Y., Kruse, Kevin, Banerjee, Avik, Hitchinson, Ben, Geyer, Melissa, Huang, Fei, Guaiquil, Victor, Mutso, Amelia A., Sanders, Martin, Rosenblatt, Mark I., Maienschein-Cline, Mark, Lawrence, Matthew S., Gaponenko, Vadim, Malik, Asrar B., Komarova, Yulia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591057/
https://www.ncbi.nlm.nih.gov/pubmed/37794584
http://dx.doi.org/10.1016/j.xcrm.2023.101223
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author Lee, Quinn
Chan, Wan Ching
Qu, Xinyan
Sun, Ying
Abdelkarim, Hazem
Le, Jonathan
Saqib, Uzma
Sun, Mitchell Y.
Kruse, Kevin
Banerjee, Avik
Hitchinson, Ben
Geyer, Melissa
Huang, Fei
Guaiquil, Victor
Mutso, Amelia A.
Sanders, Martin
Rosenblatt, Mark I.
Maienschein-Cline, Mark
Lawrence, Matthew S.
Gaponenko, Vadim
Malik, Asrar B.
Komarova, Yulia A.
author_facet Lee, Quinn
Chan, Wan Ching
Qu, Xinyan
Sun, Ying
Abdelkarim, Hazem
Le, Jonathan
Saqib, Uzma
Sun, Mitchell Y.
Kruse, Kevin
Banerjee, Avik
Hitchinson, Ben
Geyer, Melissa
Huang, Fei
Guaiquil, Victor
Mutso, Amelia A.
Sanders, Martin
Rosenblatt, Mark I.
Maienschein-Cline, Mark
Lawrence, Matthew S.
Gaponenko, Vadim
Malik, Asrar B.
Komarova, Yulia A.
author_sort Lee, Quinn
collection PubMed
description Wet age-related macular degeneration (AMD), characterized by leaky neovessels emanating from the choroid, is a main cause of blindness. As current treatments for wet AMD require regular intravitreal injections of anti-vascular endothelial growth factor (VEGF) biologics, there is a need for the development of less invasive treatments. Here, we designed an allosteric inhibitor of end binding-3 (EB3) protein, termed EBIN, which reduces the effects of environmental stresses on endothelial cells by limiting pathological calcium signaling. Delivery of EBIN via eye drops in mouse and non-human primate (NHP) models of wet AMD prevents both neovascular leakage and choroidal neovascularization. EBIN reverses the epigenetic changes induced by environmental stresses, allowing an activation of a regenerative program within metabolic-active endothelial cells comprising choroidal neovascularization (CNV) lesions. These results suggest the therapeutic potential of EBIN in preventing the degenerative processes underlying wet AMD.
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spelling pubmed-105910572023-10-24 End binding-3 inhibitor activates regenerative program in age-related macular degeneration Lee, Quinn Chan, Wan Ching Qu, Xinyan Sun, Ying Abdelkarim, Hazem Le, Jonathan Saqib, Uzma Sun, Mitchell Y. Kruse, Kevin Banerjee, Avik Hitchinson, Ben Geyer, Melissa Huang, Fei Guaiquil, Victor Mutso, Amelia A. Sanders, Martin Rosenblatt, Mark I. Maienschein-Cline, Mark Lawrence, Matthew S. Gaponenko, Vadim Malik, Asrar B. Komarova, Yulia A. Cell Rep Med Article Wet age-related macular degeneration (AMD), characterized by leaky neovessels emanating from the choroid, is a main cause of blindness. As current treatments for wet AMD require regular intravitreal injections of anti-vascular endothelial growth factor (VEGF) biologics, there is a need for the development of less invasive treatments. Here, we designed an allosteric inhibitor of end binding-3 (EB3) protein, termed EBIN, which reduces the effects of environmental stresses on endothelial cells by limiting pathological calcium signaling. Delivery of EBIN via eye drops in mouse and non-human primate (NHP) models of wet AMD prevents both neovascular leakage and choroidal neovascularization. EBIN reverses the epigenetic changes induced by environmental stresses, allowing an activation of a regenerative program within metabolic-active endothelial cells comprising choroidal neovascularization (CNV) lesions. These results suggest the therapeutic potential of EBIN in preventing the degenerative processes underlying wet AMD. Elsevier 2023-10-03 /pmc/articles/PMC10591057/ /pubmed/37794584 http://dx.doi.org/10.1016/j.xcrm.2023.101223 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Lee, Quinn
Chan, Wan Ching
Qu, Xinyan
Sun, Ying
Abdelkarim, Hazem
Le, Jonathan
Saqib, Uzma
Sun, Mitchell Y.
Kruse, Kevin
Banerjee, Avik
Hitchinson, Ben
Geyer, Melissa
Huang, Fei
Guaiquil, Victor
Mutso, Amelia A.
Sanders, Martin
Rosenblatt, Mark I.
Maienschein-Cline, Mark
Lawrence, Matthew S.
Gaponenko, Vadim
Malik, Asrar B.
Komarova, Yulia A.
End binding-3 inhibitor activates regenerative program in age-related macular degeneration
title End binding-3 inhibitor activates regenerative program in age-related macular degeneration
title_full End binding-3 inhibitor activates regenerative program in age-related macular degeneration
title_fullStr End binding-3 inhibitor activates regenerative program in age-related macular degeneration
title_full_unstemmed End binding-3 inhibitor activates regenerative program in age-related macular degeneration
title_short End binding-3 inhibitor activates regenerative program in age-related macular degeneration
title_sort end binding-3 inhibitor activates regenerative program in age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591057/
https://www.ncbi.nlm.nih.gov/pubmed/37794584
http://dx.doi.org/10.1016/j.xcrm.2023.101223
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