Matrix metalloproteinase-3 (MMP-3)-mediated gene therapy for glaucoma.

Approximately 80 million people globally are affected by glaucoma, with a projected increase to over 110 million by 2040. Substantial issues surrounding patient compliance remain with topical eye drops, and up to 10% of patients become treatment resistant, putting them at risk of permanent vision loss. The major risk factor for glaucoma is elevated intraocular pressure, which is regulated by the balance between the secretion of aqueous humor and the resistance to its flow across the conventional outflow pathway. Here, we show that adeno-associated virus 9 (AAV9)-mediated expression of matrix metalloproteinase-3 (MMP-3) can increase outflow in two murine models of glaucoma and in nonhuman primates. We show that long-term AAV9 transduction of the corneal endothelium in the nonhuman primate is safe and well tolerated. Last, MMP-3 increases outflow in donor human eyes. Collectively, our data suggest that glaucoma can be readily treated with gene therapy-based methods, paving the way for deployment in clinical trials

Genetic and environmental risk factors in age-related macular degeneration in vitro, in vivo and population studies

THESIS 10017The aims of this project are to show the potential sites of interaction between underlying genetic susceptibilities and environmental influences (cigarette smoke) in neovascular AMD. Our current hypothesis proposes that cigarette smoke exerts its toxic effects by altering the expression of vasoactive proteins at the level of the RPE, ultimately promoting angiogenesis. To test this we used in vitro and in vivo menthods. We also consider the possibility that known genetic risk factors in regions coding for vasoactive proteins may contribute to this process of angiogenesis in Irish patients with AMD. [exerpt Page 69

Structural and dynamic parameters obtained from (17)O NMR, EPR, and NMRD studies of monomeric and dimeric Gd(3)+ complexes of interest in magnetic resonance imaging: an integrated and theoretically self-consistent approach(1)

D. Hugh Powell, Orla M. Ni Dhubhghaill, Dirk Pubanz, Lothar Helm, Yakob S. Lebedev, Willi Schlaepfer, and André E. Merbac