Involvement of oxidative stress and mitochondrial dysfunction in the osmotic swelling of retinal glial cells from diabetic rats.
Osmotic swelling of retinal glial (Müller) cells may contribute to the development of edema in diabetic retinopathy. Here, we tested whether oxidative stress and mitochondrial dysfunction are pathogenic factors involved in the osmotic swelling of Müller cells in retinal slices from control and streptozotocin-injected hyperglycemic rats. Hypotonic challenge did not change the size of Müller cell somata from control animals but induced soma swelling in Müller cells of diabetic animals. Administration of a reducing agent blocked the osmotic swelling of Müller cell somata. In retinal tissues from control animals, administration of the reducing agent blocked also the swelling-inducing effects of antagonists of P2Y₁ and adenosine A₁ receptors. In tissues from diabetic animals, inhibition of xanthine oxidase decreased the soma swelling by approximately 50% while inhibition of NADPH oxidase and nitric oxide synthase had no effects. Blockade of mitochondrial oxidative stress by perindopril, as well as of mitochondrial permeability transition by cyclosporin A or minocycline, attenuated the swelling. In addition, activation of mitochondrial K(ATP) channels by pinacidil fully prevented the swelling. The data suggest that oxidative stress produced by xanthine oxidase, as well as the mitochondria, are implicated in the induction of osmotic swelling of Müller cells from diabetic rats.
Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany.
Katja
K
Krügel
Antje
A
Wurm
Thomas
T
Pannicke
Margrit
M
Hollborn
Anett
A
Karl
Peter
P
Wiedemann
Andreas
A
Reichenbach
Leon
L
Kohen
Andreas
A
Bringmann
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009457:Neuroglia / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018384:Oxidative Stress; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D055351:Retinal Neurons / Q000187:drug effects / Q000473:pathology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D058921:Purinergic P2Y Receptor Antagonists; D043682:Receptor, Adenosine A1; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D019255:NADPH Oxidases