Ocular adenovirus gene transfer varies in efficiency and inflammatory response

Teresa Borrás, Ernst R. Tamm, J. Samuel Zigler

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. To study the effects of adenoviral gene transfer to the tissue 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 108 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 μ1 Av1LacZ4 (8 x 108 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 tissue of the anterior segment and emphasize the need to address the inflammatory response to these first- generation adenoviral vectors.

Original languageEnglish (US)
Pages (from-to)1282-1293
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number7
StatePublished - Jun 1 1996

Keywords

  • adenovirus
  • anterior segment cells
  • gene transfer
  • inflammation
  • lens organ cultures

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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