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A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing

Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may...

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Autores principales: Barone, Francesca, Amaral, Juan, Bunea, Irina, Farnoodian, Mitra, Gupta, Rohan, Gupta, Rishabh, Baker, Dara, Phillips, M. Joseph, Blanch, Richard J., Maminishkis, Arvydas, Gamm, David M., Bharti, Kapil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393234/
https://www.ncbi.nlm.nih.gov/pubmed/37288665
http://dx.doi.org/10.1172/jci.insight.157654
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author Barone, Francesca
Amaral, Juan
Bunea, Irina
Farnoodian, Mitra
Gupta, Rohan
Gupta, Rishabh
Baker, Dara
Phillips, M. Joseph
Blanch, Richard J.
Maminishkis, Arvydas
Gamm, David M.
Bharti, Kapil
author_facet Barone, Francesca
Amaral, Juan
Bunea, Irina
Farnoodian, Mitra
Gupta, Rohan
Gupta, Rishabh
Baker, Dara
Phillips, M. Joseph
Blanch, Richard J.
Maminishkis, Arvydas
Gamm, David M.
Bharti, Kapil
author_sort Barone, Francesca
collection PubMed
description Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may slow down vision loss in late stages of age-related macular degeneration (AMD), a polygenic disease induced by RPE atrophy. However, accelerated development of effective cell therapies is hampered by the lack of large-animal models that allow testing safety and efficacy of clinical doses covering the human macula (20 mm(2)). We developed a versatile pig model to mimic different types and stages of retinal degeneration. Using an adjustable power micropulse laser, we generated varying degrees of RPE, PR, and CC damage and confirmed the damage by longitudinal analysis of clinically relevant outcomes, including analyses by adaptive optics and optical coherence tomography/angiography, along with automated image analysis. By imparting a tunable yet targeted damage to the porcine CC and visual streak — with a structure similar to the human macula — this model is optimal for testing cell and gene therapies for outer retinal diseases including AMD, retinitis pigmentosa, Stargardt, and choroideremia. The amenability of this model to clinically relevant imaging outcomes will facilitate faster translation to patients.
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spelling pubmed-103932342023-08-02 A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing Barone, Francesca Amaral, Juan Bunea, Irina Farnoodian, Mitra Gupta, Rohan Gupta, Rishabh Baker, Dara Phillips, M. Joseph Blanch, Richard J. Maminishkis, Arvydas Gamm, David M. Bharti, Kapil JCI Insight Technical Advance Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may slow down vision loss in late stages of age-related macular degeneration (AMD), a polygenic disease induced by RPE atrophy. However, accelerated development of effective cell therapies is hampered by the lack of large-animal models that allow testing safety and efficacy of clinical doses covering the human macula (20 mm(2)). We developed a versatile pig model to mimic different types and stages of retinal degeneration. Using an adjustable power micropulse laser, we generated varying degrees of RPE, PR, and CC damage and confirmed the damage by longitudinal analysis of clinically relevant outcomes, including analyses by adaptive optics and optical coherence tomography/angiography, along with automated image analysis. By imparting a tunable yet targeted damage to the porcine CC and visual streak — with a structure similar to the human macula — this model is optimal for testing cell and gene therapies for outer retinal diseases including AMD, retinitis pigmentosa, Stargardt, and choroideremia. The amenability of this model to clinically relevant imaging outcomes will facilitate faster translation to patients. American Society for Clinical Investigation 2023-06-08 /pmc/articles/PMC10393234/ /pubmed/37288665 http://dx.doi.org/10.1172/jci.insight.157654 Text en © 2023 Barone et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Technical Advance
Barone, Francesca
Amaral, Juan
Bunea, Irina
Farnoodian, Mitra
Gupta, Rohan
Gupta, Rishabh
Baker, Dara
Phillips, M. Joseph
Blanch, Richard J.
Maminishkis, Arvydas
Gamm, David M.
Bharti, Kapil
A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing
title A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing
title_full A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing
title_fullStr A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing
title_full_unstemmed A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing
title_short A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing
title_sort versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing
topic Technical Advance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393234/
https://www.ncbi.nlm.nih.gov/pubmed/37288665
http://dx.doi.org/10.1172/jci.insight.157654
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