Gene Therapy for Eye Diseases

Eye diseases are disorders that affect the structure or function of the eye, leading to vision impairment or blindness. These conditions can be classified into various types, including inherited, infectious, degenerative, neoplastic, traumatic, or autoimmune. Eye diseases pose a significant threat to the quality of life and well-being of millions of people worldwide. Current treatments for eye diseases encompass pharmacological, surgical, and optical interventions; however, they are often constrained by low efficacy, high cost, or adverse effects. Gene therapy, as an emerging and promising approach, aims to treat eye diseases by delivering therapeutic genes to target cells or tissues, either to correct a genetic defect or enhance a biological function.

Principle of Gene Therapy for Eye Diseases

Gene therapy is rooted in the principle of delivering therapeutic genes to the target cells or tissues of the eye, with the goal of correcting genetic defects or enhancing biological functions. Gene therapy relies on a gene vector, which serves as a vehicle for carrying and delivering the gene of interest to the target site. These gene vectors can be categorized as either viral or non-viral, depending on their origin from viruses or not. Viral vectors offer high transduction efficiency but may also entail safety concerns, such as immunogenicity, toxicity, or insertional mutagenesis. Non-viral vectors exhibit lower transduction efficiency but are safer, more cost-effective, and easier to produce. Various methods of gene delivery can be employed in gene therapy, including intravitreal injection, subretinal injection, electroporation, or gene editing. These methods vary in terms of their specificity, invasiveness, and applicability. Gene therapy also encompasses gene expression regulation, which involves controlling the amount and timing of gene expression in the target cells or tissues. This regulation can be achieved using different promoters, enhancers, or silencers, as well as through the use of inducible or repressible systems. Proper gene expression regulation is critical for achieving optimal therapeutic effects while minimizing adverse outcomes.

Advantages of Gene Therapy for Eye Diseases

Gene therapy possesses several characteristics that render it a promising approach for treating eye diseases. One key feature is its high specificity, enabling precise targeting of specific cells or tissues within the eye, such as the retina, cornea, or optic nerve, based on the type and cause of the eye disease. Moreover, gene therapy can pinpoint particular genes or pathways implicated in the disease's pathogenesis or progression, including those encoding photoreceptors, enzymes, growth factors, or cytokines. Another significant advantage lies in gene therapy's enduring impact. It can yield sustained or permanent therapeutic effects following just a single or a few administrations. This lasting effect is achieved by integrating the therapeutic gene into the target cells' genome or by employing non-integrating vectors that persist in the cells over an extended period. Furthermore, gene therapy boasts a high level of safety, minimizing the risk of adverse effects or complications often associated with other treatments. This safety is ensured through the use of safe and efficient gene vectors, optimization of gene delivery methods, and meticulous regulation of gene expression levels and duration. Gene therapy's precise targeting, long-lasting effects, and safety measures make it a highly promising and advantageous solution for various eye diseases.

Research Progress in Gene Therapy for Eye Diseases

Gene therapy has made remarkable strides in the realm of eye diseases, featuring significant advancements in both preclinical and clinical studies. Several gene therapy products and trials have received approval or are currently underway to address a spectrum of eye conditions, including inherited retinal dystrophies, age-related macular degeneration, glaucoma, corneal dystrophies, and uveitis. One noteworthy example is Luxturna, the pioneering gene therapy product sanctioned by the FDA for treating Leber congenital amaurosis, a rare inherited retinal dystrophy leading to severe vision impairment or blindness. Luxturna utilizes an adeno-associated virus (AAV) vector to deliver a functional copy of the RPE65 gene to retinal pigment epithelium cells, restoring the production of a crucial enzyme for the visual cycle. Clinical studies have demonstrated Luxturna's efficacy in enhancing visual function and the quality of life in patients with RPE65 mutations. Another significant development is RGX-314, a gene therapy product presently undergoing phase III clinical trials for the treatment of wet age-related macular degeneration, a prevalent degenerative eye disease causing vision loss due to abnormal blood vessel growth and leakage in the macula. RGX-314 employs an AAV vector to deliver a gene encoding a monoclonal antibody fragment that binds and inhibits vascular endothelial growth factor (VEGF), a pivotal factor in angiogenesis and vascular permeability. Research findings indicate that RGX-314 reduces the necessity for anti-VEGF injections and enhances visual acuity in patients with wet AMD. These examples showcase the promising outcomes gene therapy has achieved or is poised to achieve in the realm of eye diseases. The progress in this field underscores the potential of gene therapy as a groundbreaking solution for diverse ocular conditions.

Table 1. Gene Therapy for Eye Diseases: A Summary of Selected Products and Trials

References

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