Abstract
Primary open angle glaucoma (POAG) and infantile aphakic glaucoma (IAG) are significant contributors of vision loss in adults and infants respectively. Both indications are associated with fibrosis of the trabecular meshwork (TM) that attenuates aqueous humor outflow, elevated intraocular pressure (IOP) and retinal ganglion cell (RGC) death. Transforming growth factor β2 (TGFβ2) is implicated in epithelial to mesenchymal transition (EMT) in both POAG and IAG. A major regulator of TGFβ2 is decorin, a proteoglycan whose expression is reduced in glaucoma patients. In this study we demonstrate highly efficient infection of the murine anterior chamber including ciliary body, corneal stroma, TM and corneal nerves using the adeno-associated virus (AAV) vector AAV-IKV. Intracameral injection of AAV-IKV expressing a constitutively active TGFβ2 (AAV-IKV-TGFβ2CS) led to fibrosis of the TM in mice and a subsequent increase in IOP and RGC death, modeling pathophysiological features of POAG and IAG. Expression of human decorin from an AAV-IKV vector (AAV-IKV-Decorin) attenuated fibrosis, IOP and RGC death in AAV-IKV-TGFβ2CS injected mice, suggesting that AAV-IKV-Decorin may function as a therapy for POAG and IAG respectively. Finally, intracameral injection of an AAV-IKV-GFP vector in a non-human primate led to expression of GFP in the cornea without any discernible toxicity.