Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
Virscio, New Haven, CT, USA.
Gene Ther. 2023 Sep;30(9):714-722. doi: 10.1038/s41434-023-00407-z. Epub 2023 May 24.
While many studies have investigated the use of recombinant adeno-associated vectors (rAAV) in the posterior chamber for treatment of inherited retinal diseases, fewer studies have looked at rAAV's ability to transduce cells within the anterior chamber. This study focuses on evaluating the tropism and tolerability of three rAAV serotypes-rAAV2/6, rAAV2/9, and rAAV2/2[MAX]-expressing a green fluorescent protein (GFP) reporter following intracameral injection in the non-human primate (NHP) African green monkey (Chlorocebus sabaeus) model. Injection of high dose (1 × 10 vg/eye) rAAV vector resulted in transient inflammation characterized by aqueous flare and cellular infiltrate that resolved without intervention in all serotypes. Post-mortem histology revealed widespread expression of GFP in cells of the trabecular meshwork and iris in high dose rAAV2/6, rAAV2/9, and particularly rAAV2/2[MAX] eyes, indicating that rAAV vectors of these serotypes have broad tropism for cells of the anterior chamber and may facilitate the treatment of blinding disorders, such as glaucoma.
虽然许多研究已经调查了重组腺相关病毒（rAAV）在后房治疗遗传性视网膜疾病中的应用，但很少有研究关注 rAAV 在眼前房内转导细胞的能力。本研究主要评估了三种 rAAV 血清型（rAAV2/6、rAAV2/9 和 rAAV2/2[MAX]）在非人类灵长类动物（NHP）非洲绿猴（Chlorocebus sabaeus）模型中经前房内注射后对 GFP 报告基因的亲嗜性和耐受性。高剂量（1×10 vg/眼）rAAV 载体注射后，所有血清型均出现短暂炎症，表现为房水闪辉和细胞浸润，未经干预即可消退。死后组织学检查显示，高剂量 rAAV2/6、rAAV2/9 和 rAAV2/2[MAX]眼的小梁网和虹膜细胞中广泛表达 GFP，表明这些血清型的 rAAV 载体对前房细胞具有广泛的亲嗜性，可能有助于治疗青光眼等致盲性疾病。
