title: Manganese porphyrin reduces retinal injury induced by ocular hypertension in rats.
abstract: This study aimed to clarify the possible therapeutic benefit of preferential nitric oxide synthase (NOS) inhibition and catalytic antioxidant Mn (III) meso-tetrakis (N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP(5+)) treatment in a rat model of elevated intraocular pressure (EIOP). Rats were randomly divided into different experimental groups which received either intraperitoneal MnTnHex-2-PyP(5+) (0.1 mg/kg/day), intragastric NOS inhibitor (S-methylthiourea: SMT; 5 mg/kg/day) or both agents for a period of 6 weeks. Ocular hypertension was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. Neuroprotective effects of given treatments were determined via electrophysiological measurements of visual evoked potentials (VEP) while retina and vitreous levels of MnTnHex-2-PyP(5+) were measured via LC-MS/MS. Latencies of all VEP components (P(1), N(1), P(2), N(2), P(3)) were significantly prolonged (p < 0.05) in EIOP and returned to control levels following all three treatment protocols. Ocular hypertension significantly increased retinal protein nitration (p < 0.001) which returned to baseline levels in all treated groups. NOS-2 expression and nitrate/nitrite levels were significantly greater in non-treated rats with EIOP. Retinal TUNEL staining showed apoptosis in all ocular hypertensive rats. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of MnTnHex-2-PyP(5+) treatment and NOS inhibition in ocular hypertension.
authors.affiliation: Department of Biochemistry, Akdeniz University Medical School, Campus, 07070 Antalya, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Dogan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Unal
authors.forename: Nihal
authors.initials: N
authors.lastname: Ozturk
authors.forename: Piraye
authors.initials: P
authors.lastname: Yargicoglu
authors.forename: Aysegul
authors.initials: A
authors.lastname: Cort
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Ines
authors.initials: I
authors.lastname: Batinic-Haberle
authors.forename: Mutay
authors.initials: M
authors.lastname: Aslan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005074:Evoked Potentials, Visual / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007429:Intraocular Pressure; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009798:Ocular Hypertension / Q000150:complications*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism / Q000503:physiopathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D053719:Tandem Mass Spectrometry; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008665:Metalloporphyrins; C521294:Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin; D009566:Nitrates; D009573:Nitrites; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium