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
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retinal Degeneration
/
Genetic Therapy
/
Cadherins
/
Retinal Rod Photoreceptor Cells
/
Retinal Cone Photoreceptor Cells
/
Disease Models, Animal
/
Cadherin Related Proteins
/
Nerve Tissue Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Mol Ther
Journal subject:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Year:
2024
Document type:
Article
Country of publication:
United States