Gene therapy and genome editing in ophthalmology: new frontiers in the treatment of hereditary retinal dystrophies]

Abstract

Hereditary Retinal Dystrophies (HRDs), including Retinitis Pigmentosa and Leber Congenital Amaurosis, represent a heterogeneous group of rare, progressive diseases often leading to irreversible blindness. Historically, therapeutic approaches were limited to symptomatic management and visual rehabilitation. However, the exponential advancement of genetics and molecular biology has revolutionized Ophthalmology, introducing gene therapy as a promising curative modality. This scientific article aims to critically analyze and discuss the efficacy, challenges, and translational potential of therapies based on gene replacement and genome editing (CRISPR-Cas9) for monogenic HRDs. The methodology consists of an in-depth review of phase I/II and III clinical trials, with emphasis on the mechanism of action of adeno-associated viral vectors (AAVs) and the precision of CRISPR technology for in vivo mutation correction. Clinical results demonstrate that gene therapy, as exemplified by the use of voretigene neparvovec (Luxturna), can restore visual function in patients with specific mutations. However, regulatory challenges, vector immunogenicity, and the need for more efficient delivery systems for genome editing in dominant HRDs remain crucial barriers. It is concluded that Ophthalmology is positioned at the forefront of precision medicine, with the potential to transform previously incurable diseases into treatable conditions, requiring the clinical ophthalmologist to master the principles of genomics.