Efficiency and toxicity of gene delivery to the anterior segment of rabbits

T. Borrás, E. Tamm, J. S. Zigler

Research output: Contribution to journalArticle

Abstract

Purpose: To study the delivery of active proteins into anterior segment tissues of rabbits using adenoviral gene transfer techniques. Methods: Rabbits were injected once into the anterior chamber with 20 μl of Av1LacZ4 (8 × 108 particle forming units) using a 50 μl Hamilton syringe and a 1 cm beveled 301/2G needle. Eight rabbits received the virus in the right eye while the contralateral eyes were injected with vehicle. Four of the rabbits were also treated on both eyes with 0.25% Fluoromethalone 3 times a day for the duration of the experiment. Two more animals received vehicle on one eye white the contralateral remained uninjected. Gene transfer was evaluated at 48 hours by a detailed morphological study of the residential cells containing the active delivered enzyme. Results: Gene transfer was very evident in corneal endothelium, iris anterior surface and trabecular meshwork while no transfer was observed inside the capsulated tens. Viral receptors were present in the nontransformed rabbit lens epithelial cell line N10003 and in primary rat lens epithelial explants. Presence of the virus did not affect lens transparency or provoke external discomfort signs. Infected corneal endothelial cells appeared swollen and partly detached. 3 of the 8 infected eyes showed a severe inflammatory response in chamber angle, anterior uvea and limbal conjunctiva. Conclusions: These findings indicate distinct gene transfer potentials for various tissues of the anterior segment and emphasize the need to address the inflammatory response to these first generation adenoviral vectors. The results stress the importance of designing customized vectors and delivery conditions for each tissue to be targeted. Control of inflammation by manipulating viral concentrations and modifying existing vectors will require further studies.

Original languageEnglish (US)
Pages (from-to)S10
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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