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Andrew David Jerome, Kate Israel, Pushpa Rao, Subhash Gaddipati, Susmit Suvas; Role of Vasoactive Intestinal Peptide (VIP) in modulating Herpes Simplex Virus-1 (HSV-1) induced corneal lesion. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1851.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal infection with herpes simplex virus -1 (HSV-1) could lead to the development of a chronic immunoinflammatory condition called Herpetic Stromal Keratitis (HSK). The purpose of this study was to examine the role of vasoactive intestinal peptide (VIP) in reducing the development of severe HSK lesions in the C57BL/6 mouse model.
C57BL/6 mice aged 8-12 weeks were used for corneal HSV-1 infections. Experimental techniques used were flow cytometry, Enzyme-linked Immunosorbent assay (ELISA) of tissue lysates, semi-quantitative polymerase chain reaction (PCR) of corneal tissue, immunofluorescence of frozen corneal sections, and viral titration of corneal swabs. Systemic and localized treatment of VIP was given as intra-peritoneal or subconjunctival injections, respectively. Corneal opacity (scored from 0-5) and angiogenesis (scored from 0-16) were measured with a hand-held slit lamp.
Our data demonstrates the presence of VIP in both naïve and HSV-1 infected corneas. In naïve corneas, VIP is largely localized in the corneal endothelium, whereas in the infected corneas, VIP staining was noted in the corneal stroma. With VIP receptors, VPAC1 is expressed at higher levels than VPAC2 on both CD45+ and CD45-ve cell populations. Intra-peritoneal (i.p.) administration of rVIP (5nm) given from day -1 through day 2 or day 4 post-infection reduced the influx of innate immune cells in infected corneas resulting in an increased viral load at early (day 3), but not late time-point (day 5) post-infection. On the other hand, rVIP treatment given from day 5 post-infection resulted in the development of encephalitis in more than 50% of infected mice. Unexpectedly, both systemic (i.p.) and subconjunctival injection of rVIP did not decrease the severity of HSK lesions. In fact, VIP treatment resulted in an increased incidence of eyes with severe HSK lesions when compared with the PBS treated control group.
Our results concur with the immunosuppressive property of VIP as its administration during active viral replication increases the viral load in infected corneas. The ongoing research is examining the immunosuppressive action of VIP in trigeminal ganglia to determine the underlying mechanism for the development of encephalitis and an increased incidence of severe HSK in VIP treated groups.
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