Müller cells as players in retinal degeneration and edema.
BACKGROUND
Under normal conditions, Müller cells support neuronal activity and the integrity of the blood-retinal barrier, whereas gliotic alterations of Müller cells under pathological conditions may contribute to retinal degeneration and edema formation. A major function of Müller cells is the fluid absorption from the retinal tissue, which is mediated by transcellular water transport coupled to currents through potassium channels.


METHODS
Alterations of retinal Müller cells under pathological conditions were investigated by immunohistochemistry and recording their behavior under osmotic stress.


RESULTS
In animal models of various retinopathies, e.g., retinal ischemia, ocular inflammation, retinal detachment, and diabetes, it was found that Müller cells decrease the expression of their major potassium channel (Kir4.1). This alteration is associated with an impairment of the rapid water transport across Müller cell membranes, as recognizable in the induction of cellular swelling under hypoosmolar conditions. Osmotic swelling of Müller cells is also induced by oxidative stress and by inflammatory mediators such as arachidonic acid and prostaglandins.


CONCLUSIONS
The data suggest that a disturbed fluid transport through Müller cells is (in addition to vascular leakage) a pathogenic factor contributing to the development of retinal edema. Pharmacological re-activation of the retinal water clearance by Müller cells may represent an approach to the development of new edema-resolving drugs. Triamcinolone acetonide, which is clinically used to resolve edema, prevents osmotic swelling of Müller cells as it induces the release of endogenous adenosine and subsequent A1 receptor activation which results in the opening of ion channels. Apparently, triamcinolone resolves edema by both inhibition of vascular leakage and stimulation of retinal fluid clearance by Müller cells.
Reichenbach
Andreas
A
Paul Flechsig Institute of Brain Research, Faculty of Medicine, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany.
Wurm
Antje
A
Pannicke
Thomas
T
Iandiev
Ianors
I
Wiedemann
Peter
P
Bringmann
Andreas
A
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy / Q000378:metabolism*; D009457:Neuroglia / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D012162:Retinal Degeneration / Q000188:drug therapy / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000627:therapeutic use
D005938:Glucocorticoids; D014222:Triamcinolone Acetonide