Reduction of retinal albumin leakage by the antioxidant calcium dobesilate in streptozotocin-diabetic rats.
Calcium dobesilate stabilizes blood-retinal barrier in patients with diabetic retinopathy and possesses antioxidant properties in the retinas of rats with streptozotocin-induced diabetes, exposed ex vivo to ischemia-reperfusion. Here we investigated the action of calcium dobesilate on retinal albumin leakage in streptozotocin-diabetic rats, together with relevant in vivo retinal antioxidant and permeability markers, i.e., carboxymethyl-lysine-advanced glycation end product (CML-AGE) formation and vascular endothelial cell growth factor (VEGF) overexpression. Twenty days after streptozotocin administration, diabetic rats were treated for 10 days with calcium dobesilate (100 mg/kg/day per os) or vehicle. Retinal albumin leakage, CML-AGE formation, and VEGF overexpression were evaluated by immunohistochemistry of frozen eye sections. Diabetic rats exhibited dramatic increases in: (i) retinal albumin leakage (31% of positive vessels vs. 0.2% in nondiabetic rats, P<0.008), (ii) CML-AGE retinal occurrence (40+/-3% vs. undetectable positive vessels), and (iii) retinal VEGF protein expression (14.6+/-1.1 vs. 3.5+/-0.5 VEGF-positive spots/field, P<10(-4)). Calcium dobesilate significantly reduced: (i) retinal albumin leakage (by 70%, P<0.008), (ii) retinal CML-AGEs contents (by 62%, P<0.008), and (iii) retinal VEGF expression (by 69.4%, P<0.008). In conclusion, calcium dobesilate orally given to diabetic rats markedly reduced retinal hyperpermeability, CML-AGE contents, and VEGF overexpression. These results strongly suggest that calcium dobesilate stabilizes blood-retinal barrier in diabetic retinopathy via an in situ antioxidant action. Further studies in patients are required to confirm such view.
Rota
Rossella
R
Children's Hospital Bambino Gesu, IRCCS, Rome, Italy.
Chiavaroli
Carlo
C
Garay
Ricardo P
RP
Hannaert
Patrick
P
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D002123:Calcium Dobesilate / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006490:Hemostatics / Q000494:pharmacology; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000418:Albumins; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D006490:Hemostatics; D042461:Vascular Endothelial Growth Factor A; D002123:Calcium Dobesilate; D008239:Lysine