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Review
. 2024 Jun 3;14(6):a041652.
doi: 10.1101/cshperspect.a041652.

The Extraordinary Phenotypic and Genetic Variability of Retinal and Macular Degenerations: The Relevance to Therapeutic Developments

Isabelle Audo  1   2 , Marco Nassisi  3   4   5 , Christina Zeitz  3 , José-Alain Sahel  3   2   6
Affiliations
Review

The Extraordinary Phenotypic and Genetic Variability of Retinal and Macular Degenerations: The Relevance to Therapeutic Developments

Isabelle Audo et al. Cold Spring Harb Perspect Med. .

Abstract

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of rare conditions leading to various degrees of visual handicap and to progressive blindness in more severe cases. Besides visual rehabilitation, educational, and socio-professional support, there are currently limited therapeutic options, but the approval of the first gene therapy product for RPE65-related IRDs raised hope for therapeutic innovations. Such developments are facing obstacles intrinsic to the disease and the affected tissue including the extreme phenotypic and genetic variability of IRDs and the fine tuning of visual processing through the complex architecture of the postmitotic neural retina. A precise phenotypic characterization is required prior to genetic testing, which now relies on high-throughput sequencing. Their challenges will be discussed within this article as well as their implications in clinical trial design.

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