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Jason C. Lim, Wennan Lu, Jonathan M. Beckel, Edward J. Macarak, Alan M. Laties, Claire H. Mitchell; Mechanosensitive Release Of Cytokines And Chemokines From Isolated Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5458.
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© ARVO (1962-2015); The Authors (2016-present)
The mechanical strain induced by increased intraocular pressure (IOP) can damage retinal cells, with inflammatory signals being key aspects of this response. While astrocytes have a role, we asked whether ganglion cells could themselves contribute. This study asked whether mechanical strain triggered a release of cytokines and chemokines directly from isolated retinal ganglion cells.
Isolated immunopanned retinal ganglion cells were grown on silicone substrates. Cells were stretched for 4 min at 4.1% strain followed by 1 min at 0% strain with the cycle repeated thrice over 15 min. Samples of extracellular solution were taken before and after stretch and levels of inflammatory mediators were determined using a rat antibody cytokine array. Lactose dehydrogenase (LDH) was determined by a colorimetric coupled reaction.
Stretching isolated ganglion cells led to a significant increase in the extracellular levels of numerous cytokines and chemokines. The largest increase was found for IL-3 (1.6 fold), CXCL9 (1.5 fold), TNF-α (1.5 fold) and VEGF (1.4 fold; all p<0.001). IL-1β, IL-4, IL-6, CXCL7, L-selectin and LIX were also significantly higher in the bath after stretch (p<0.01). Extracellular levels of LDH were not changed after stretch, implying that the increase in cytokines and chemokines represented a physiological release.
This study demonstrates that isolated retinal ganglion cells can release various cytokines and chemokines upon application of mechanical strain. It should be noted that relative changes represent release from non-confluent neurons into a large bath area, and elevations in situ are expected to be substantially higher.
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