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

• Vinores, S. A. ^[1] ; Derevjanik, N. L. ^[1] ; Shi, A. ^[1] ; Vinores, M. A. ^[1] ; Klein, D. A. ^[1] ; Whittum-Hudson, J. A. ^[2]
  1. [1] Johns Hopkins University

     Johns Hopkins University

     Estados Unidos

     
  2. [2] Department s of Internal Medicine, Immunology and Microbiology, and Ophthalmology, Wayne Slate University School of Medicine, Detroit, Michigan, USA
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 16, Nº. 4, 2001, págs. 1061-1071
• Idioma: inglés
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• Resumen

  • Expe rimental herpesvirus retino p athy pr esents a unique mode l o f a tr ans ient inflammato ry res ponse in the virus-injec ted eye and subsequent acute re tina l necrosis and c hr o ni c infla mma ti o n in the contrala te ra l eye. For 6 days afte r infectio n, VEGF. TGH\ , a nd T GF132 were associa te d only with inflammatory cells in the injected eye. By 6 days (after v ir a l a ntigens were no lo nger de tected), VEGF and TGF132 were upregulated in retinas of injected eyes until 8-10 d ays. In contra la te ra l eyes, VEG F was f irs t demo nstra ted in the re tina at 6-7 days ( prio r to the appea rance of viral antigens) and TGF132 at 7-8 days. Staining for these factors was also evident around areas of necrosis. T he VEGF recepto r, fit-I, was associated with ganglio n cells and the inner nuclea r l ayer of nor mal a nd expe rimental mice and it was a lso de mo nstr ated around areas of nec ros is. Another VEG F recept or, flk-], was localized to MUlle r cell processes and the oute r p lexiform layer in norma l a nd expe rime nt a l mice. Coinc ident w ith VEGF upregulatio n in the retinas of herpesvirus- l injected mice, there was increased flk-1 in ganglion cells and the inner and outer nuclea r l ayers. IL-6 was associa te d w ith Mulle r cell e ndfeet in nor ma l mice. Following unilateral intraocular inoculation, IL-6 spread a lo ng the Miille r cell processes a nd some astrocytes demonstrated IL-6 in both eyes at 6-8 days. T he present study d e mo ns trates t hat intraocul a r inoculatio n o f herpesvirus is sufficient to induce VEGF, flk-l, TGFI32, and IL-6 in the retinas of injected a nd co ntra late ra l eyes. Furthe r investigatio n o f commo n sig naling pathways for these factors during res po nses to vira l infectio n and the develo pment o f acute retina l nec rosis could provide information useful for therapeutic interventio n in human herpesviru retino pathy.