Gene Therapy
摘要
Gene therapy has emerged as a transformative approach in the treatment of inherited and acquired ocular diseases. The eye presents a highly favorable target for gene therapy due to its immune-privileged environment, compartmentalized anatomy, and the availability of non-invasive methods for clinical monitoring. Advances in molecular genetics have identified numerous gene mutations responsible for retinal dystrophies such as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), and Stargardt disease, paving the way for targeted genetic interventions. Adeno-associated virus (AAV) vectors are the most widely used delivery vehicles in ocular gene therapy, offering efficient and sustained expression of therapeutic genes with minimal toxicity. Subretinal and intravitreal injections are commonly employed routes of administration, each with specific advantages depending on the target cell population. The success of voretigene neparvovec (Luxturna), the first FDA-approved gene therapy for RPE65-related LCA, has validated the clinical potential of this modality and spurred development of similar treatments. Innovative genome-editing technologies such as CRISPR/Cas9 are further expanding the therapeutic horizon by enabling precise correction of pathogenic mutations in situ. Beyond monogenic disorders, gene therapy is being explored for complex conditions like age-related macular degeneration and glaucoma, using strategies that modulate angiogenesis, neuroprotection, or intraocular pressure. Despite the promise, challenges remain, including vector capacity limitations, immunogenicity, and long-term safety concerns. Continued research and clinical trials are critical to optimize delivery systems, broaden therapeutic applications, and ensure durability of response. Gene therapy holds immense potential to prevent vision loss and restore sight in patients with previously untreatable ocular conditions.