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. 2003 Sep 17;64(1):71–81. doi: 10.1016/0165-5728(95)00156-5

Modulation of immune-associated surface markers and cytokine production by murine retinal glial cells

Kristen M Drescher a, Judith A Whittum-Hudson b,∗
PMCID: PMC7119802  PMID: 8598392

Abstract

Murine retinal glia are normally negative for major histocompatibility complex (MHC) Class II antigens and express low levels of MHC Class I and intercellular adhesion molecule-1 (ICAM-1) as detected by avidin-biotin-peroxidase immunohistochemistry. These surface molecules associated with immune function were either induced (Class II) or upregulated (Class I and ICAM-1) on cultured retinal glial cells in a dose- and time-dependent manner following exposure to recombinant Interferonγ (rIFN-γ). MHC Class I and II expression by passaged and primary cells was maximal (> 90% positive) after incubation with 100 U/ml of rlFN-y for 48 h. ICAM-1 expression by primary and passaged cells tripled between 48 and 72 h after exposure to 25 or 50 U/ml of rIFN-γ. By 72 h after exposure to 100 U/ml of rIFN-y, 62% of the retinal glia were positive for ICAM-1, whereas under normal culture conditions these molecules were detected on < 3% of the retinal glia. Bacterial lipopolysaccharide (LPS), a known stimulator of central nervous system (CMS) astrocytes, increased ICAM-1 expression only 3-fold to 9% of cells staining positively, but neither MHC Class I nor Class II expression was altered from baseline levels. Surface expression of ICAM-1, MHC Class I, and MHC Class II was unaffected by exposure to either rTNF-α (1000 U/ml) or rIL-6 (100 U/ml) for 24 h. Under normal culture conditions, intracellular interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected immunohistochemically. Exposure to either rIFN-γ or LPS induced more intense staining which correlated with increased secreted levels of both cytokines in culture supernatants. Levels of secreted TNF-α increased 6-fold after stimulation with LPS for 24 h, while secreted IL-6 increased over 9-fold. These results support the hypothesis that retinal glia may participate in intraretinal immune processes following stimulation during inflammatory and infectious processes via either cell surface- or soluble mediator-dependent mechanisms or a combination of both.

Keywords: Müller cells, Retina, Glia, Intercellular adhesion molecule-1, Interferon- y, Major histocompatibility complex antigens, Cytokines, Mouse, Interleukin-6, Tumor necrosis factor-α

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