Quesada Erika, Rojas Sofía, Campos Xiomara, Wu Lihteh
Asociados de Mácula, Vítreo y Retina de Costa Rica, Primer Piso Torre Mercedes Paseo Colón, San José, Costa Rica.
Graefes Arch Clin Exp Ophthalmol. 2025 Apr 28. doi: 10.1007/s00417-025-06837-2.
Neovascular age-related macular degeneration (NV-AMD) is a leading cause of preventable blindness in the elderly. Intravitreal injections of anti-VEGF agents are currently the treatment of choice for NV-AMD. However this treatment is burdensome and fosters non-compliance which leads to inferior visual outcomes. Gene therapy has emerged as a promising therapeutic option for NV-AMD that may improve these outcomes. Potential risks of gene therapy include a potential immune response that may be elicited by the vector, accidental activation of oncogenes or inactivation of tumor suppresor genes leading to malignant transformation via insertational mutagenesis and integration of the viral DNA inserts into the host's DNA. The main strategy of current gene therapy for NV-AMD has focused on delivering transgenes that express anti-angiogenic proteins that directly or indirectly inhibit the VEGF pathway. Ixoberogene soroparvovec, RGX-314 and 4D-150 are the leading NV-AMD genetic treatment programs. Pre-clinical models suggest that genome surgery with clustered regularly interspaced short palindromic repeats (CRISPR) may be another option in the future.
新生血管性年龄相关性黄斑变性（NV-AMD）是老年人可预防失明的主要原因。玻璃体内注射抗VEGF药物是目前NV-AMD的首选治疗方法。然而，这种治疗负担沉重且会导致患者依从性差，从而导致视力预后不佳。基因治疗已成为一种有前景的NV-AMD治疗选择，可能会改善这些预后。基因治疗的潜在风险包括载体可能引发的潜在免疫反应、致癌基因的意外激活或肿瘤抑制基因的失活，导致通过插入诱变和病毒DNA插入片段整合到宿主DNA中而发生恶性转化。目前用于NV-AMD的基因治疗的主要策略集中在递送表达直接或间接抑制VEGF途径的抗血管生成蛋白的转基因。Ixoberogene soroparvovec、RGX-314和4D-150是主要的NV-AMD基因治疗方案。临床前模型表明，使用成簇规律间隔短回文重复序列（CRISPR）进行基因组手术可能是未来的另一种选择。
