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Abstract #5452 Published in IGR 1-2
Adenoviral reporter gene transfer to the human trabecular meshwork does not alter aqueous humor outflow. Relevance for potential gene therapy of glaucoma
Borras T; Rowlette LL; Erzurum SC; Epstein DLGene Therapy 1999; 6: 515-524
Obstruction of the aqueous humor outflow from the anterior chamber of the eye leads to an elevation of intraocular pressure in glaucoma, the second major cause of blindness worldwide. Our goal is to be able to modulate aqueous humor outflow resistance by gene transfer to the cells of the trabecular meshwork (TM). We have previously shown that adenoviral vectors are able to transfer a reporter gene to the TM of post-mortem human donors. However, assessing gene therapy for glaucoma requires models that can monitor changes in aqueous humor outflow facility (C = flow/pressure). In this study we used four replication-deficient adenoviruses in two such perfusion models. In the first model, whole porcine eyes were infected, perfused at constant pressure and flow changes recorded for 5 h. In the second one, anterior segments from human eyes were infected, perfused at constant flow and pressure changes recorded for 3 days. A single dose of 10 sup(8) adenovirus plaque forming units (pfu) causes a reduction in C while single doses of 10 sup(7) 10 sup(6) and 10 sup(5) p.f.u. do not affect outflow facility and retain positive gene transfer These findings indicate that adenovirus, at effective doses, could become useful vectors far gene therapy of glaucoma.
T. Borras, Duke University Medical Center, Wadsworth Building, Erwin Road, Durham, NC 27710; United States
Classification:
11.9 Gene therapy (Part of: 11 Medical treatment)
