LOCALIZATION OF TUMOR-NECROSIS-FACTOR RECEPTOR MESSENGER-RNA IN NORMAL AND HERPES-SIMPLEX VIRUS-INFECTED MOUSE EYES

Purpose. To investigate the distribution of p75 and p55 tumor necrosis factor receptor (TNFR) mRNA in normal mouse eyes and in mouse eyes ac utely infected with McKrae strain herpes simplex virus (HSV). Methods. In situ hybridization with antisense S-35-labeled riboprobes for p55 and p75 TNFR subtypes was used in uninfected and HSV-infected mouse ey es. Controls included the use of sense riboprobes and corneas inoculat ed with vehicle alone. Results. In uninfected and infected mouse eyes, in situ hybridization produced an autoradiographic signal for mRNA, e ncoding both p75 and p55 over the corneal endothelium, iris, ciliary b ody, choroid, and arachnoid layers of the optic nerve sheath. In addit ion, the signal was observed over scattered cells at the vitreoretinal interface. Signal for p75, but not p55, was observed over cells in th e retinal ganglion cell layer. Acute HSV infection was accompanied by an intense leukocytic infiltrate in the conjunctiva, the corneal subep ithelium and stroma, the anterior and posterior chambers, the iris roo t and ciliary body, and the vitreous cavity. In this setting, increase d p75 and p55 mRNA signal was correlated closely with the number and l ocation of receptor-bearing white blood cells. Signal over control sec tions hybridized With sense p75 and p55 TNFR cRNA probes was comparabl e to background. Signal over control eyes inoculated with sterile vehi cle showed slight increased signal in the immediate vicinity of the tr aumatic keratitis, but otherwise it was comparable to that observed in uninfected animals. Conclusions. The observed distribution of p75 and p55 TNFR mRNA in normal and acutely infected mouse eyes, and particul arly over the heavily vascularized uveal tract and over cells at the v itreoretinal interface, supports a role for TNF as a mediator of intra ocular inflammation, perhaps as a key regulator of the blood-ocular ba rrier.