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

Stanley A. Vinores, N. L. Derevjanik, A. Shi, M. A. Vinores, D. A. Klein, J. A. Whittum Hudson


Experimental herpesvirus retinopathy presents a unique model of a transient inflammatory response in the virus-injected eye and subsequent acute retinal necrosis and chronic inflammation in the contralateral eye. For 6 days after infection, VEGF, TGFβ, and TGFβ2 were associated only with inflammatory cells in the injected eye. By 6 days (after viral antigens were no longer detected), VEGF and TGFβ2 were upregulated in retinas of injected eyes until 8-10 days. In contralateral eyes, VEGF was first demonstrated in the retina at 6-7 days (prior to the appearance of viral antigens) and TGFβ2 at 7-8 days. Staining for these factors was also evident around areas of necrosis. The VEGF receptor, flt- l, was associated with ganglion cells and the inner nuclear layer of normal and experimental mice and it was also demonstrated around areas of necrosis. Another VEGF receptor, flk-l, was localized to Miiller cell processes and the outer plexiform layer in normal and experimental mice. Coincident with VEGF upregulation in the retinas of herpesvirus-l injected mice, there was increased flk-l in ganglion cells and the inner and outer nuclear layers. IL- 6 was associated with Miiller cell endfeet in normal mice. Following unilateral intraocular inoculation, 1L-6 spread along the Miiller cell processes and some astrocytes demonstrated IL-6 in both eyes at 6-8 days. The present study demonstrates that intraocular inoculation of herpesvirus is sufficient to induce VEGF, flk-l, TGFβ2, and IL-6 in the retinas of injected and contralateral eyes. Further investigation of common signaling pathways for these factors during responses to viral infection and the development of acute retinal necrosis could provide information useful for therapeutic intervention in human herpesvirus retinopathy.


vascular endothelial growth factor; transforming growth factor β; interleukin 6; herpesvirus; retinopathy

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