title: Effect of ocular hypertension on retinal nitridergic pathway activity.
abstract: OBJECTIVE
  Understanding the mechanisms of neuronal cell death in glaucoma is important for devising new treatments. Excitatory amino acids, excessive Ca(2+) influx, and formation of nitric oxide (NO) via NO synthase (NOS)-1 could be involved in glaucomatous neuropathy. The purpose of the present study was to examine the retinal nitridergic pathway activity in rats exposed to experimentally elevated intraocular pressure.
  
  
  METHODS
  Weekly injections of HA were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with saline solution. At 3 or 6 weeks of treatment, retinal NOS activity was assessed through the conversion of (3)H-L-arginine to (3)H-L-citrulline, whereas NOS-1, -2, and -3 levels were assessed by Western blotting. L-Arginine uptake was measured using (3)H-l-arginine, whereas mRNA levels of L-arginine transporters were determined by semiquantitative RT-PCR. In addition, cyclic guanosine monophosphate (cGMP) levels were quantified by radioimmunoassay.
  
  
  RESULTS
  At both 3 and 6 weeks of treatment, NOS activity significantly increased in HA-injected eyes although no changes in retinal NOS-1, -2, or -3 levels were observed in eyes injected with HA. L-Arginine influx and mRNA levels of cationic amino acid transporter type (CAT)-1 and -2 significantly increased in retinas from hypertensive eyes. Retinal cGMP levels significantly increased in eyes injected with HA for 3 but not 6 weeks.
  
  
  CONCLUSIONS
  These results suggest a significant activation of the retinal nitridergic pathway in hypertensive eyes.
authors: Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Universidad de Buenos Aires, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors: Nicolás
authors: N
authors: Belforte
authors: María Cecilia
authors: MC
authors: Moreno
authors: Cora
authors: C
authors: Cymeryng
authors: Melina
authors: M
authors: Bordone
authors: María Inés
authors: MI
authors: Keller Sarmiento
authors: Ruth E
authors: RE
authors: Rosenstein
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D001120:Arginine / Q000378:metabolism; D015153:Blotting, Western; D002956:Citrulline / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D006820:Hyaluronic Acid / Q000633:toxicity; D007429:Intraocular Pressure; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009798:Ocular Hypertension / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D026923:Amino Acid Transport Systems, Basic; D012333:RNA, Messenger; D002956:Citrulline; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D006152:Cyclic GMP