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C. R. Brandt, M. M. Sauter, S. Cai, B. T. Gabelt, P. L. Kaufman; IL-6 Induction by HSV and AdV Vector Challenge of Monkey Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5923.
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Intracameral or intravitreal delivery of HSV-1 and AdV vectors induces a transient inflammation in the primate eye. The overall goal is to identify the trigger. To that end, we have identified the cells secreting IL-6 in monkey retina tissue exposed to HSV-1 and AdV vectors.
Monkey retina tissue was exposed to the HSV-1 vector hrR3, which expresses β-gal, wild type HSV-1 KOS, AdICP6, an AdV expressing the large subunit of the HSV-1 RR protein, or AdLacZ, an AdV expressing β-gal, for 24hours. Supernatants were harvested and analyzed for IL-6 expression by ELISA. Retina tissue was fixed, paraffin embedded, and sectioned for immunofluorescence (IF). Sections were stained with antibodies to Il-6, Arrestin-C, γ-synuclein, and NF-ΚB. Supernatants from retina exposed to hrR3 were titered to determine if viral replication occurred.
Increased levels of Il-6 were detected in the supernatant of retina tissue exposed to hrR3, compared to the control. Exposure to KOS increased Il-6 secretion, but to a lesser extent than hrR3. Exposure to AdICP6 or AdLacZ did not cause a significant induction of IL-6 in the supernatant. IF with an IL-6 antibody demonstrated that hrR3, and to a lesser extent KOS or AdV, challenge induced Il-6 in cone and retinal ganglion cells. Double label IF with antibodies to cone (Arrestin C) or ganglion (γ-synuclein) cell markers confirmed that these cell types secrete Il-6 in response to vector challenge. IF with an anti-NFΚB (p65) antibody demonstrated that NFΚB is activated and translocates to the nucleus in retina tissue exposed to both HSV and AdV. The hrR3 vector did not replicate in retinal tissue.
The results indicate that IL-6 is induced in cone and ganglion cells of monkey retina in response to challenge with HSV or AdV vectors. Exposure to vector virus also results in activation and nuclear translocation of the transcription factor NF-ΚB. These results raise the possibility that IL-6 may be involved in the vector induced inflammatory response in the primate eye.
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