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Journal of Virology, October 2004, p. 11327-11333, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11327-11333.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transient Immunosuppression Stops Rejection of Virus-Transduced Enhanced Green Fluorescent Protein in Rabbit Retina

Kentaro Doi,1 Jian Kong,1 Janos Hargitai,1 Stephen P. Goff,2 and Peter Gouras1*

Departments of Ophthalmology,1 Biochemistry & Molecular Biology and Howard Hughes Medical Institute, College of Physicians & Surgeons, Columbia University, New York, New York2

Received 13 January 2004/ Accepted 9 June 2004

The expression of lentivirus-transduced enhanced green fluorescent protein (EGFP) was detectable in rabbit retinal pigment epithelium (RPE) within 3 to 5 days after subretinal injection of the vector. Within 2 to 3 weeks, EGFP-expressing cells were eliminated by rejection. In the current experiments, we monitor serum antibody titers for EGFP before and after transduction and determine whether systemic immunosuppression prevents recognition of EGFP by the immune system. While all control rabbits developed antibodies against EFGP and showed signs of rejection, no such evidence was observed with animals which received immunosuppression. One month of systemic immunosuppression permanently prevented rejection of RPE with EGFP expression. Fluorescence has been maintained for more than a year. If a control eye was injected with the same virus after terminating immunosuppression, both eyes showed signs of rejection. The lack of rejection is not due to tolerance but to a failure of the animals to detect the foreign protein. Detection must depend upon a brief window of time after surgery needed to introduce the vector, perhaps related to a concurrent but transient inflammation. This strategy may be useful in managing other types of rejection in the retina.

* Corresponding author. Mailing address: Department of Ophthalmology, College of Physicians & Surgeons, Columbia University, 630 W. 168th St., New York, NY 10032. Phone: (212) 305-5688. Fax: (212) 305-9087. E-mail: pg10{at}columbia.edu.

Journal of Virology, October 2004, p. 11327-11333, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11327-11333.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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