Effects of intraocular injection of a low concentration of zinc on the rat retina.
The main aim of this study was to investigate whether intraocular injection of low concentrations of zinc (no greater than 10 microM) aid the survival of ganglion cells in the rat retina after excitotoxic (NMDA) and ischemia/reperfusion injuries. We also determined whether low amounts of zinc cause any detectable retinal toxicity. Intraocular injection of NMDA caused substantial reductions in the mRNA levels of the ganglion cell-specific markers Thy-1 and neurofilament light (NF-L). Co-injection of 0.1 or 1 nmol zinc neither diminished nor exacerbated the effect of NMDA on the levels of these mRNAs. Likewise, ischemia/reperfusion caused significant decreases in the levels of Thy-1 and NF-L mRNAs and in the b-wave amplitude of the electroretinogram. These effects were not counteracted by injection of zinc. Intraocular injection of NMDA caused marked toxicological effects in retinal glial cells, including upregulations of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glial fibrial acidic protein (GFAP), basic fibroblast growth factor (FGF-2) and ciliary neurotrophic factor (CNTF). Interestingly, injection of 1 nmol zinc caused no changes in the levels of COX-2 and iNOS, yet produced similar, although quantitatively less pronounced, changes in FGF-2, GFAP and CNTF. The upregulations of FGF-2 and CNTF suggest that increasing zinc intake may benefit injured retinal neurons. However, this was not found to be the case in the present studies, perhaps due to the acute nature of the injury paradigms utilised.
Nakamichi
N
N
Laboratory of Molecular Pharmacology, Kanazawa University Graduate School of Natural Science and Technology, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan.
Chidlow
G
G
Osborne
N N
NN
D000818:Animals; D001252:Astringents / Q000494:pharmacology*; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000235:genetics; D051546:Cyclooxygenase 2; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004596:Electroretinography / Q000295:instrumentation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005123:Eye; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics; D016202:N-Methylaspartate / Q000633:toxicity; D009457:Neuroglia / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000276:immunology; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D018800:Thy-1 Antigens / Q000235:genetics; D013997:Time Factors; D019287:Zinc Sulfate / Q000494:pharmacology*
D001252:Astringents; D020934:Ciliary Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D016222:Fibroblast Growth Factor 2; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D019287:Zinc Sulfate; D012243:Rhodopsin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases