Rescue of cone and rod photoreceptor function in a CDHR1-model of age-related retinal degeneration.
Mol Ther
; 32(5): 1445-1460, 2024 May 01.
Article
em En
| MEDLINE
| ID: mdl-38504520
ABSTRACT
Age-related macular degeneration (AMD) is the most common cause of untreatable blindness in the developed world. Recently, CDHR1 has been identified as the cause of a subset of AMD that has the appearance of the "dry" form, or geographic atrophy. Biallelic variants in CDHR1-a specialized protocadherin highly expressed in cone and rod photoreceptors-result in blindness from shortened photoreceptor outer segments and progressive photoreceptor cell death. Here we demonstrate long-term morphological, ultrastructural, functional, and behavioral rescue following CDHR1 gene therapy in a relevant murine model, sustained to 23-months after injection. This represents the first demonstration of rescue of a monogenic cadherinopathy in vivo. Moreover, the durability of CDHR1 gene therapy seems to be near complete-with morphological findings of the rescued retina not obviously different from wildtype throughout the lifespan of the mouse model. A follow-on clinical trial in patients with CDHR1-associated retinal degeneration is warranted. Hypomorphic CDHR1 variants may mimic advanced dry AMD. Accurate clinical classification is now critical, as their pathogenesis and treatment are distinct.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Degeneração Retiniana
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Terapia Genética
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Caderinas
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Células Fotorreceptoras Retinianas Bastonetes
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Células Fotorreceptoras Retinianas Cones
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Modelos Animais de Doenças
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Proteínas Relacionadas a Caderinas
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Proteínas do Tecido Nervoso
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido