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
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
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.