Interleukin-6 protects retinal ganglion cells from pressure-induced death.

Sappington RM, Chan M, Calkins DJ
Invest Ophthalmol Vis Sci. 2006 47 (7): 2932-42

PMID: 16799036 · DOI:10.1167/iovs.05-1407

PURPOSE - The response of retinal ganglion cells (RGCs) to ocular pressure in glaucoma likely involves signals from astrocytes and microglia. How glia-derived factors influence RGC survival at ambient and elevated pressure and whether the inflammatory cytokine interleukin-6 (IL-6) is a contributing factor were investigated.

METHODS - Primary cultures of retinal astrocytes, microglia, and RGCs were prepared using immunomagnetic separation. Comparisons were made of RGC survival at ambient and elevated pressure (+70 mm Hg) and with pressure-conditioned medium from glia with, and depleted of, IL-6.

RESULTS - Pressure elevated for 24 to 48 hours reduced RGC density, increased TUNEL labeling, and upregulated several apoptotic genes, including the early immediate genes c-jun and jun-B. Pressure-conditioned medium from astrocytes reduced RGC survival another 38%, while microglia medium returned RGC survival to ambient levels. These effects were unrelated to IL-6 in microglia medium. Neither astrocyte- nor microglia-conditioned medium affected ambient RGC survival unless depleted of IL-6, which induced a 63% and a 18% decrease in RGCs, respectively. Recombinant IL-6 equivalent to levels in glia-conditioned medium doubled RGC survival at elevated pressure.

CONCLUSIONS - For RGCs at ambient pressure, IL-6 secreted from astrocytes and microglia under pressure is adequate to abate other proapoptotic signals from these glia. For RGCs challenged by elevated pressure, decreased IL-6 in astrocyte medium is insufficient to counteract these signals. Increased IL-6 in microglia medium counters not only proapoptotic signals from these cells but also the pressure-induced apoptotic cascade intrinsic to RGCs.

MeSH Terms (22)

Animals Animals, Newborn Apoptosis Astrocytes bcl-2-Associated X Protein Cell Separation Cytoprotection Enzyme-Linked Immunosorbent Assay Hydrostatic Pressure Immunohistochemistry In Situ Nick-End Labeling Interleukin-6 Microglia Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-jun Rats Rats, Sprague-Dawley Recombinant Proteins Retinal Ganglion Cells Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Up-Regulation

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