Investigative Ophthalmology & Visual Science, Vol 37, 1282-1293, Copyright © 1996 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Ocular adenovirus gene transfer varies in efficiency and inflammatory response

T Borras, ER Tamm and JS Zigler Jr
Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, National Institutes of health, Bethesda, Maryland 20892, USA.

PURPOSE. To study the effects of adenoviral gene transfer to the tissues of the anterior segment in vitro by rat and monkey lens organ cultures and in vivo by single injection into the anterior chamber of rabbits. METHODS. In vitro, intact lens cultures were exposed to 1 to 4 x 10(8) pfu Av1LacZ4 and Av1Luc1 in TC199 medium containing no serum or growth factors. Av1LacZ4 and Av1Luc1 are replication-deficient adenovirus vectors, carrying the reporter genes Escherichia coli LacZ and firefly luciferase, respectively. In vivo, the anterior chambers of eight rabbits were injected once with 20 mumol Av1LacZ4 (8 x 10(8) pfu) and evaluated 48 hours after injection. Enzyme activity of the reporter genes was measured biochemically and histochemically. RESULTS. In organ cultures, adenovirus delivers reporter genes efficiently to the ciliary processes but penetrates poorly into the capsulated lenses. Viral receptors, however, are present in rat lens epithelium, as in primary trabecular meshwork and other lens cell lines. In vivo, gene transfer was evident in corneal endothelium, iris anterior surface, and trabecular meshwork. Presence of the virus did not affect lens transparency or provoke external discomfort signs. Infected corneal endothelial cells were swollen and partly detached; 3 of 8 infected eyes showed a severe inflammatory response in chamber angle, anterior uvea, and limbal conjunctiva. CONCLUSIONS. These findings reveal the distinct gene transfer potential of each of the tissues of the anterior segment and emphasize the need to address the inflammatory response to these first-generation adenoviral vectors.

This article has been cited by other articles:

				W. Xue, R. Wallin, E. A. Olmsted-Davis, and T. Borras Matrix GLA Protein Function in Human Trabecular Meshwork Cells: Inhibition of BMP2-Induced Calcification Process. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 997 - 1007. [Abstract] [Full Text] [PDF]

				C F Jessup, H M Brereton, D J Coster, and K A Williams In vitro adenovirus mediated gene transfer to the human cornea Br. J. Ophthalmol., June 1, 2005; 89(6): 658 - 661. [Abstract] [Full Text] [PDF]

				N. Wajih, T. Borras, W. Xue, S. M. Hutson, and R. Wallin Processing and Transport of Matrix {gamma}-Carboxyglutamic Acid Protein and Bone Morphogenetic Protein-2 in Cultured Human Vascular Smooth Muscle Cells: EVIDENCE FOR AN UPTAKE MECHANISM FOR SERUM FETUIN J. Biol. Chem., October 8, 2004; 279(41): 43052 - 43060. [Abstract] [Full Text] [PDF]

				C. R. Ethier, S. Wada, D. Chan, and W. D. Stamer Experimental and Numerical Studies of Adenovirus Delivery to Outflow Tissues of Perfused Human Anterior Segments Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1863 - 1870. [Abstract] [Full Text] [PDF]

				T. Borras, C. R. Brandt, R. Nickells, and R. Ritch Gene Therapy for Glaucoma: Treating a Multifaceted, Chronic Disease Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2513 - 2518. [Full Text] [PDF]

				M.-L. Tsai, S.-L. Chen, P.-I Chou, L.-Y. Wen, R. J.-F. Tsai, and Y.-P. Tsao Inducible Adeno-Associated Virus Vector-Delivered Transgene Expression in Corneal Endothelium Invest. Ophthalmol. Vis. Sci., March 1, 2002; 43(3): 751 - 757. [Abstract] [Full Text] [PDF]

				C. Kee, S. Sohn, and J.-M. Hwang Stromelysin Gene Transfer into Cultured Human Trabecular Cells and Rat Trabecular Meshwork In Vivo Invest. Ophthalmol. Vis. Sci., November 1, 2001; 42(12): 2856 - 2860. [Abstract] [Full Text] [PDF]

				S. A. Rayner, D. F. P. Larkin, and A. J. T. George TNF Receptor Secretion after Ex Vivo Adenoviral Gene Transfer to Cornea and Effect on In Vivo Graft Survival Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1568 - 1573. [Abstract] [Full Text]

				A. J. T. GEORGE, C. V. ARANCIBIA-CARCAMO, H. M. AWAD, R. M. COMER, Z. FEHEVARI, W. J. KING, M. KADIFACHI, T. HUDDE, C. KEROUEDAN-LEBOSSE, F. MIRZA, et al. Gene Delivery to the Corneal Endothelium Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S194 - 200. [Abstract] [Full Text] [PDF]

				B. Spencer, S. Agarwala, M. Miskulin, M. Smith, and C. R. Brandt Herpes Simplex Virus-Mediated Gene Delivery to the Rodent Visual System Invest. Ophthalmol. Vis. Sci., May 1, 2000; 41(6): 1392 - 1401. [Abstract] [Full Text]

				R R ALI, M B REICHEL, D M HUNT, and S S BHATTACHARYA Gene therapy for inherited retinal degeneration Br. J. Ophthalmol., September 1, 1997; 81(9): 795 - 801. [Full Text] [PDF]