title: 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.
abstract: Recombinant E1-deleted adenoviral vectors (DeltaE1-Ad) are promising tools for in vivo gene transfer into the mammalian CNS including the retina. However, the duration of transgene expression is limited, and this limitation has partly been attributed to an immune response directed against vector-derived proteins. Here, we employed immunocytochemistry to assess the immune response to intravitreously injected DeltaE1-Ad encoding the lacZ gene or various neurotrophins (NTs). beta-Galactosidase was expressed by retinal cells for up to 4 weeks. Following intravitreal inoculation of AdCMV-lacZ, microglial and T cells were detected with a panel of antibodies in the retinal cell layers after 2 days (D2). The inflammatory response reached a maximum between D7 and D14. In contrast, no immune response was seen following injection of Ad encoding NTs. Yet, like with Ad-CMV-lacZ, their expression was also limited to approximately 4 weeks. Thus, beta-galactosidase seems to trigger a host immune response following intravitreal adenoviral lacZ gene transfer, but immune responses are not the cause of limited NT transgene expression from the CMV promoter in the inner retina.
authors.affiliation: Department of Neurology, University of Tübingen, D-72076, Tübingen, Germany. stefan.isenmann@uni-tuebingen.de
authors.forename: S
authors.initials: S
authors.lastname: Isenmann
authors.forename: S
authors.initials: S
authors.lastname: Engel
authors.forename: S
authors.initials: S
authors.lastname: Kügler
authors.forename: C
authors.initials: C
authors.lastname: Gravel
authors.forename: M
authors.initials: M
authors.lastname: Weller
authors.forename: M
authors.initials: M
authors.lastname: Bähr
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D002452:Cell Count; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D007763:Lac Operon / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D017628:Microglia / Q000276:immunology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D020933:Neurotrophin 3 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D012160:Retina / Q000276:immunology*; D019076:Transgenes / Q000235:genetics*; D014822:Vitreous Body / Q000821:virology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3