Evidence for induction of interferon-alpha and interferon-beta in retinal glial cells of Müller

Studies were performed to determine if retinal glial cells of Müller transcribe the genes for interferon-alpha (IFNalpha) or IFNbeta upon exposure to virus. Responses to herpes simplex virus type 1 (HSV-1) were tested with cultured murine Müller cells and, in vivo, with retinas obtained after bilateral injection of either HSV-1 or buffer into the anterior chamber of the eyes of BALB/c mice. Induction of IFN transcription and relative temporal changes in transcript levels occurred over time after either in vitro or in vivo exposure to HSV-1. Transcription of both IFN genes was induced in cultured glia within 1 hr after exposure to virus. IFN transcripts were detected in retinas by 24 hr postinfection and these were maximal at 3 days. By in situ hybridization (ISH), IFNalpha2 mRNA localized to focal areas in the intact retinas of virus-injected eyes and was consistent with our previous report of a transient, focal appearance of viral antigens in those retinas. Uninfected cells and ocular tissues were negative for IFN transcripts. Combined ISH and immunohistochemistry on retinal impression smears confirmed that glial fibrillary acidic protein-positive Müller cells are an intraretinal source of IFNalpha and IFNbeta transcripts after ocular exposure to HSV-1. Our results support a role for Muller cells as participants in intraretinal antiviral or immunomodulatory responses via type 1 IFN production and may have implications for future therapeutic interventions.