PMID- 12941377 OWN - NLM STAT- MEDLINE DCOM- 20031219 LR - 20190726 IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 45 IP - 5 DP - 2003 Oct TI - Effects of intraocular injection of a low concentration of zinc on the rat retina. PG - 637-48 AB - 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. FAU - Nakamichi, N AU - Nakamichi N AD - Laboratory of Molecular Pharmacology, Kanazawa University Graduate School of Natural Science and Technology, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan. FAU - Chidlow, G AU - Chidlow G FAU - Osborne, N N AU - Osborne NN LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Astringents) RN - 0 (Ciliary Neurotrophic Factor) RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Isoenzymes) RN - 0 (RNA, Messenger) RN - 0 (Thy-1 Antigens) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 6384-92-5 (N-Methylaspartate) RN - 6LR8C1B66Q (Dizocilpine Maleate) RN - 7733-02-0 (Zinc Sulfate) RN - 9009-81-8 (Rhodopsin) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos1 protein, rat) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases) SB - IM MH - Animals MH - Astringents/*pharmacology MH - Cell Death MH - Cell Survival/drug effects MH - Ciliary Neurotrophic Factor/genetics MH - Cyclooxygenase 2 MH - Dizocilpine Maleate/pharmacology MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Electroretinography/instrumentation/methods MH - Excitatory Amino Acid Agonists/toxicity MH - Excitatory Amino Acid Antagonists/pharmacology MH - Eye MH - Fibroblast Growth Factor 2/genetics/metabolism MH - Glial Fibrillary Acidic Protein/genetics/metabolism MH - Immunoblotting MH - Immunohistochemistry MH - Isoenzymes/genetics MH - N-Methylaspartate/toxicity MH - Neuroglia/drug effects MH - Nitric Oxide Synthase/genetics/immunology MH - Nitric Oxide Synthase Type I MH - Nitric Oxide Synthase Type II MH - Prostaglandin-Endoperoxide Synthases/genetics MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/genetics/metabolism/physiopathology MH - Retina/cytology/*drug effects MH - Retinal Ganglion Cells/*drug effects MH - Reverse Transcriptase Polymerase Chain Reaction MH - Rhodopsin/genetics/metabolism MH - Thy-1 Antigens/genetics MH - Time Factors MH - Zinc Sulfate/*pharmacology EDAT- 2003/08/28 05:00 MHDA- 2003/12/20 05:00 CRDT- 2003/08/28 05:00 PHST- 2003/08/28 05:00 [pubmed] PHST- 2003/12/20 05:00 [medline] PHST- 2003/08/28 05:00 [entrez] AID - S0028390803002065 [pii] AID - 10.1016/s0028-3908(03)00206-5 [doi] PST - ppublish SO - Neuropharmacology. 2003 Oct;45(5):637-48. doi: 10.1016/s0028-3908(03)00206-5.