Physiologic properties of Müller cells from human eyes affected with uveal melanoma.
OBJECTIVE
To study physiologic characteristics of human Müller 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 Müller cells. The Müller 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 Müller 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 Müller cells from healthy organ donors. By contrast, Müller 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 Müller 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 Müller cells. Hypotonic stress induced Müller 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 Müller cells.
Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig, Leipzig, Germany.
Antje
A
Grosche
Thomas
T
Pannicke
Anett
A
Karl
Ianors
I
Iandiev
Mike
M
Francke
Peter
P
Wiedemann
Andreas
A
Reichenbach
Andreas
A
Bringmann
D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012165:Retinal Ganglion Cells / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000473:pathology / Q000503:physiopathology*; D000098943:Uveal Melanoma