Cytokine profiles and inflammatory cells during HSV-1-induced acute retinal necrosis

Abstract

PURPOSE. To investigate infiltrating cells, cytokines, and kinetics of cytokine expression during acute retinal necrosis (ARN) in the uninoculated eye after inoculation of herpes simplex virus (HSV)-1 into the anterior chamber of one eye of BALB/c mice. METHODS. At different time points after inoculation of 2 × 104 plaque-forming units (PFU) HSV-1 (KOS strain) or an equivalent volume of Vero cell extract in cell culture medium, the uninoculated eyes were enucleated. RT-PCRs for TNFα, IFNγ, and IL-4 and immunohistochemical staining were performed to identify infiltrating cells and cytokines. Cytometric bead array was used to measure the levels of TNFα, IFNγ, and IL-4 protein. RESULTS. CD4+ T cells, F4/80 + macrophages, Gr-1+ polymorphonuclear cells (PMNs), and CD19+ B cells were detected in the uninoculated eye of virus-infected mice. Furthermore, RPE65+ retinal pigment epithelial (RPE) cells and activated Müller cells were also detected in the ARN lesion. TNFα, IFNγ, and IL-4 mRNA and protein were upregulated during the evolution of ARN in HSV-1-infected contralateral eyes compared with levels in control subjects. Immunohistochemistry revealed that cytokines were produced by infiltrating cells as well as by resident retinal cells. CONCLUSIONS. The results of these studies support the idea that T cells and cytokines are actively involved in HSV-1 retinitis. They also suggest that PMNs, B cells, and/or macrophages, as well as resident retinal cells, such as RPE and activated Müller cells, also play a role in the pathogenesis of HSV-1 retinitis. Copyright © Association for Research in Vision and Ophthalmology.