1. Adeno-Associated Viral Vector 2 and 9 Transduction Is Enhanced in Streptozotocin-Induced Diabetic Mouse Retina
- Author
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Sanjar Madrakhimov, Tae Kwann Park, Ha Yan Park, Keerang Park, Si Hyung Lee, and Jin Young Yang
- Subjects
0301 basic medicine ,lcsh:QH426-470 ,viruses ,adeno-associated virus ,Biology ,medicine.disease_cause ,Retinal ganglion ,Article ,Viral vector ,03 medical and health sciences ,chemistry.chemical_compound ,Transduction (genetics) ,0302 clinical medicine ,Genetics ,medicine ,lcsh:QH573-671 ,Molecular Biology ,Adeno-associated virus ,Retina ,lcsh:Cytology ,Retinal ,Diabetic retinopathy ,Streptozotocin ,medicine.disease ,Molecular biology ,gene therapy ,lcsh:Genetics ,diabetic retinopathy ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,diabetes mellitus ,Molecular Medicine ,sense organs ,medicine.drug - Abstract
Adeno-associated viruses (AAVs) are currently the most popular vector platform technology for ocular gene therapy. While transduction efficiency and tropism of intravitreally administered AAV has been fairly well established in various retinal conditions, its transduction pattern in diabetic retinas has not previously been characterized. Here, we describe the transduction efficiencies of four different AAV serotypes, AAV2, 5, 8, and 9, in streptozotocin (STZ)-induced diabetic mouse retinas after intravitreal injections, which differed according to the duration of diabetic induction. STZ was intraperitoneally injected into C57/B6 diabetic mice subjected to unilateral intravitreal injection of AAV2, AAV5, AAV8, and AAV9 packaged with EGFP. Significantly enhanced AAV2 and AAV9 transduction was observed in 2-month-old diabetic mouse retinas compared to the 2-week-old diabetic mouse retinas and nondiabetic, vector uninjected or injected retinas. Intravitreal injection of AAV5 or AAV8 serotype in 2-month- and 2-week-old diabetic mouse retinas did not show any significant vector transduction enhancement compared to the nondiabetic control retinas. The tropism of AAV2 and AAV9 in diabetic mouse retinas differed. AAV2 was transduced into various retinal cells, including Müller cells, microglia, retinal ganglion cells (RGCs), bipolar cells, horizontal cells, and amacrine cells, whereas AAV9 was effectively transduced only into RGC and horizontal cells. The expression levels of receptors and co-receptors for AAV2 and AAV9 were significantly increased in 2-month-old diabetic mouse retinas. The results of our study demonstrated that AAV2 and AAV9 may be the vector of choice in treating diabetic retinopathy (DR) with gene therapy, and DR-related retinal changes may improve AAV vector transduction efficiency. Keywords: adeno-associated virus, diabetes mellitus, diabetic retinopathy, gene therapy
- Published
- 2018