Contribution of nitric oxide-producing cells in normal and diabetic rat retina.
OBJECTIVE
To examine the immunohistochemical localization of L-arginine and L-citrulline and determine where and how nitric oxide (NO) is produced in the normal and streptozotocin (STZ)-induced diabetic rat retinas.


METHODS
NO is produced when L-arginine is changed to L-citrulline by NO synthase (NOS). In normal and STZ-induced diabetic rats, using an immunohistochemical method, we examined the retinal distribution of L-arginine and L-citrulline after intracardiac perfusion. We studied the distribution of NOS after immersed fixation and analyzed the number of neuronal NOS (nNOS)-positive neurons.


RESULTS
We observed L-arginine localization in the internal limiting membrane (ILM), the ganglion cell layer (GCL), and the inner nuclear layer (INL). L-Arginine immunoreactivity in the diabetic rat retinas was found in the inner plexiform layer (IPL), as well as in the normal retina. L-Citrulline immunoreactivity in the normal and diabetic retinas was observed in the ILM, the GCL, the IPL, and the INL. nNOS staining in the normal and diabetic rat retinas was observed in the GCL, the IPL and the INL. The number of nNOS-positive amacrine cells was less in the diabetic rat retinas.


CONCLUSIONS
NO might be produced in the GCL and amacrine cells, which show immunoreactivity to L-arginine, L-citrulline, and nNOS. In the early stage of diabetic retinopathy in STZ rat retinas, diabetes disturbed the function of the nNOS-positive amacrine cells and reduced NO production via nNOS.
Goto
Ryotaro
R
Department of Ophthalmology, Mie University School of Medicine, Mie, Japan. ryogotoh@isis.ocn.ne.jp
Doi
Motoaki
M
Ma
Ning
N
Semba
Reiji
R
Uji
Yukitaka
Y
D025042:Amacrine Cells / Q000201:enzymology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000201:enzymology*
D009419:Nerve Tissue Proteins; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat