Physiologic Properties of Muller Cells from Human Eyes Affected with Uveal Melanoma

PURPOSE. To study physiologic characteristics of human Muller cells from healthy and pathologically altered eyes. METHODS. Human tissue was used from organ donors and from patients affected with uveal melanoma. Several melanoma eyes also showed retinal detachment. Incubation of freshly prepared slices with a commercial vital dye preferentially stained Muller cells. The Muller cell response to hypotonic stress was observed by recording the cross-sectional area of cell somata. Electrophysiologic properties were investigated in parallel in whole-cell patch-clamp experiments. RESULTS. Inward K+ currents mediated by inwardly rectifying Kir channels were significantly decreased in Muller cells from eyes with uveal melanoma compared with healthy controls. This was accompanied by a decrease of the membrane potential. Both effects were stronger in cells from eyes where the melanoma had caused a widespread retinal detachment. Application of a hypotonic solution did not affect Muller cells from healthy organ donors. By contrast, Muller cells from some melanoma eyes increased their soma size in response to hypotonic solution. This effect was aggravated in cells from eyes with widespread retinal detachment. The inflammatory mediator, arachidonic acid, could induce Muller cell swelling, whereas anti-inflammatory substances reduced the swelling. CONCLUSIONS. The experiments with human tissue confirm earlier data from animal models for retinal pathologies about typical alterations of reactive Muller cells. Hypotonic stress induced Muller cell swelling preferentially in cells from melanoma-affected eyes that displayed decreased inward current amplitudes. Widespread melanoma-associated retinal detachment potentiated the pathologic alterations of Muller cells. (Invest Ophthalmol Vis Sci. 2012;53:4170-4176) DOI:10.1167/iovs.12-9746