Transduction pattern of adeno‐associated viruses in the trabecular meshwork and anterior‐segment structures in a rat model of ocular hypertension

Abstract

AbstractPurposeTo investigate transduction patterns of self‐complimentary adeno‐associated virus (scAAV) serotype 2, 5, and 8 in trabecular meshwork (TM) and anterior segment structures of ocular hypertensive (OHT) rat models.MethodsWe assessed transduction efficiencies of scAAV 2, 5, and 8 in the anterior‐segment structures of the eyes of SD rats with OHT by circumlimbal suturing, followed by intracameral injection of scAAV2, 5, or 8 packaged with EGFP, and compared with the control. Expression level of receptors for scAAV2 (perlecan and syndecan), scAAV5 (2, 3‐linked sialic acid), and scAAV8 (67kDa laminin receptor) was analyzed by using immunohistochemistry and quantitative PCR.ResultsThe transduction of scAAV2 and 5 in the TM of OHT rats was markedly enhanced after 1 month, and transduction of scAAV5 was more efficient than that of scAAV2; transduction of scAAV8 into the TM did not occur. The transduction of scAAV2, 5, and 8 was enhanced in the ciliary body, iris, and corneal endothelium of the OHT eyes for 3 months. The expression levels of receptors for scAAV2 and scAAV5 were significantly increased in the OHT compared with control eyes.ConclusionsThe results showed that scAAV 2 and 5 effectively target the ciliary body and TM in OHT eyes, and OHT related changes in anterior segment structures enhance scAAV transduction.