Vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGFß), and interleukin-6 (IL-6) in experimental herpesvirus retinopathy: association with inflammation and viral infection

Abstract

Ex pe rime nt a l he rpesv iru s retin opa th y prese nts a uniqu e model of a transient infl ammatory response in the virus-injected eye and subsequent acute retin al nec rosis a nd c hr o ni c infl amm ati o n in th e co nt ra late ral eye . For 6 days after in fec ti on, VEG F. TGH \, a nd T GF13 2 we re assoc ia ted o nl y w ith infl ammatory cells in the injected eye. By 6 days (after viral anti ge ns we re no longe r detected), VEG F and TGF132 we re upregul ated in retinas of injected eyes until 8- 10 days. In co ntr alate ra l eyes, VEG F was first demonstrated in th e re tin a at 6-7 days (pri or to th e appea rance of vira l antige ns) and TGF13 2 at 7-8 days. Staining fo r these factors was also evident around areas of necrosis. The VEGF receptor, fit-I , was associated with ganglion cells and the inner nuclear laye r of normal and ex perimental mi ce and it was also demonstrated around areas of necrosis. Another VEG F receptor, flk-] , was loca li zed to MUlle r ce ll processes and th e oute r plex ifo rm layer in no rm al and ex pe rime nta l mi ce . Coin cident with VEGF upregul ation in the retinas of herpesvirus-l injected mice, there was increased fl k-1 in ganglion ce lls and the inner and out er nuclear laye rs. IL6 was assoc iated with Mull er ce ll endfeet in normal mice. Following unilateral intraocular inocul ation, IL-6 sp read alo ng th e Miill e r ce ll processes and some astrocytes demonstra ted IL-6 in both eyes at 6-8 days. T he pr ese nt stu dy demo nstr ates that intr aoc ul a r inocul ation of herpesvirus is suffi cient to induce VEGF, flk-l , TGFI32, and IL-6 in the retin as of inj ected and contralateral eyes. Furth er investigation of common signaling pathways fo r these fac tors during responses to viral in fect ion and th e deve lopme nt of ac ute ret in al necrosis could prov ide in formation use ful fo r therapeutic intervention in human herpesviru retinopathy.