Retinal Glial (Muller) Cells: Sensing and Responding to Tissue Stretch

PURPOSE. To test whether Muller glial cells sense, and respond to, mechanical tension in the retina. METHODS. A device was designed to stretch the retina at right angles to its surface, across retinal layers. Pieces of retina were mounted between two hollow tubes, and uniaxial force was applied to the tissue using a micrometer-stepping motor. Muller cells were selectively stained with the fluorescent, calcium-sensitive dye X-Rhod-1 and were monitored in real time during retinal stretch in vitro. Immunohistochemistry was used to study protein levels and activation of intracellular pathways in stretched retinas. RESULTS. Muller cells responded acutely with transient increases in fluorescence during stretch, indicative of increased intracellular calcium levels. All the Muller cells elongated uniformly, and there was no apparent difference between retinal layers in resistance against mechanical deformation. After stretch, Muller cells showed fast activation of extracellular signal-regulated kinase (after 15 minutes), upregulation of transcription factor c-Fos (after 1 hour), and basic fibroblast growth factor (after 3 hours). No changes in intermediate filament protein expression were observed in Muller cells up to 3 hours after stretch. CONCLUSIONS. A novel technique was developed for real-time monitoring of Muller cells during retinal stretch, which allowed the identification of Muller cells as a mechanoresponsive cell type. Mechanical stress triggers molecular responses in Muller cells that could prevent retinal damage. (Invest Ophthalmol Vis Sci. 2010;51:1683-1690) DOI:10.1167/iovs.09-4159