Intravitreal adenoviral gene transfer evokes an immune response in the retina that is directed against the heterologous lacZ transgene product but does not limit transgene expression

Citation
S. Isenmann et al., Intravitreal adenoviral gene transfer evokes an immune response in the retina that is directed against the heterologous lacZ transgene product but does not limit transgene expression, BRAIN RES, 892(2), 2001, pp. 229-240
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
0006-8993 → ACNP
Volume
892
Issue
2
Year of publication
2001
Pages
229 - 240
Database
ISI
SICI code
0006-8993(20010223)892:2<229:IAGTEA>2.0.ZU;2-Z
Abstract
Recombinant E1-deleted adenoviral vectors (Delta E1-Ad) are promising tools for in vivo gene transfer into the mammalian CNS including the retina. How ever, the duration of transgene expression is limited, and this limitation has partly been attributed to an immune response directed against vector-de rived proteins. Here, we employed immunocytochemistry to assess the immune response to intravitreously injected Delta E1-Ad encoding the lacZ gene or various neurotrophins (NTs). beta -Galactosidase was expressed by retinal c ells for up to 3 weeks. Following intravitreal inoculation of AdCMV-lacZ, m icroglial and T cells were detected with a panel of antibodies in the retin al cell layers after 2 days (D2). The inflammatory response reached a maxim um between D7 and D14. In contrast, no immune response was seen following i njection of Ad encoding NTs. Yet, like with Ad-CMV-lacZ, their expression w as also limited to approximately 3 weeks. Thus, beta -galactosidase seems t o trigger a host immune response following intravitreal adenoviral lacZ gen e transfer, but immune responses are not the cause of limited NT transgene expression from the CMV promoter in the inner retina. (C) 2001 Elsevier Sci ence B.V. All rights reserved.