The glucocorticoid triamcinolone acetonide inhibits osmotic swelling of retinal glial cells via stimulation of endogenous adenosine signaling.
The glucocorticoid triamcinolone acetonide is clinically used for the treatment of macular edema. However, the edema-resolving mechanisms of triamcinolone are incompletely understood. Since cell swelling is a central cause of cytotoxic edema in the brain and retina, we determined the effects of triamcinolone acetonide on the swelling of retinal ganglion and Müller glial cells in acutely isolated retinas from rats and guinea pigs in situ. Triamcinolone acetonide (100 microM) had no effect on the swelling of ganglion cells that was evoked in isolated whole mounts of the guinea pig retina by acute application of glutamate (1 mM) or high K+ (50 mM). However, triamcinolone reversed the osmotic swelling of Müller glial cells in retinas of the rat that was observed under various experimental conditions: in retinas isolated at 3 days after transient retinal ischemia, in retinas of eyes with lipopolysaccharide-induced ocular inflammation, and in control retinas in the presence of Ba2+ (1 mM), H2O2 (200 microM), arachidonic acid (10 microM), or prostaglandin E2 (30 nM). The inhibiting effect of triamcinolone on osmotic glial cell swelling was mediated by stimulation of transporter-mediated release of endogenous adenosine and subsequent A1 receptor activation, resulting in an elevation of the intracellular cAMP level and activation of the protein kinase A, and, finally, in an opening of extrusion pathways for K+ and Cl- ions. The inhibitory effect on the cytotoxic swelling of glial cells may contribute to the fast edema-resolving effect of vitreal triamcinolone observed in human patients.
Uckermann
Ortrud
O
Paul Flechsig Institute of Brain Research, University of Leipzig, Liebigstrasse 10-14, D-04103 Leipzig, Germany.
Kutzera
Franziska
F
Wolf
Antje
A
Pannicke
Thomas
T
Reichenbach
Andreas
A
Wiedemann
Peter
P
Wolf
Sebastian
S
Bringmann
Andreas
A
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D004487:Edema / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology; D009997:Osmotic Pressure / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use*
D005938:Glucocorticoids; D014222:Triamcinolone Acetonide; D000241:Adenosine