Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785124142063812608 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10591057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT leequinn endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT chanwanching endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT quxinyan endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT sunying endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT abdelkarimhazem endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT lejonathan endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT saqibuzma endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT sunmitchelly endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT krusekevin endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT banerjeeavik endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT hitchinsonben endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT geyermelissa endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT huangfei endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT guaiquilvictor endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT mutsoameliaa endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT sandersmartin endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT rosenblattmarki endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT maienscheinclinemark endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT lawrencematthews endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT gaponenkovadim endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT malikasrarb endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration AT komarovayuliaa endbinding3inhibitoractivatesregenerativeprograminagerelatedmaculardegeneration |