Study of effects of antiglaucoma eye drops on N-methyl-D-aspartate-induced retinal damage.
OBJECTIVE
To study the effects of antiglaucoma eye drops on N-methyl-D-aspartate (NMDA)-induced retinal damage.


METHODS
Several antiglaucoma eye drops, beta-blockers, alpha/beta-blockers, an alpha1-blocker, an alpha2-agonist, and a prostaglandin derivative, were topically administrated to NMDA-treated rat eyes daily for 2 weeks, and the retinal thickness, the number of retrograde-labeled retinal ganglion cells (RGCs), and the results of a cDNA microarray analysis were studied.


RESULTS
Intravitreal administration of NMDA caused a significant decrease in the thickness of the retinal layers and induced upregulation of glial fibrillary acidic protein (GFAP). Topical administration of beta-blockers (timolol, betaxolol, and carteolol) and a prostaglandin derivative (latanoprost) showed almost no significant effects on retinal thickness, the number of RGCs, or expression of GFAP. In contrast, the alpha/beta-blockers (nipradilol and levobunolol), the alpha1-blocker (bunazosin HCl), and the alpha2-agonist (brimonidine) showed preservation effects on retinal thickness and the number of RGCs, and marked suppression of NMDA-induced upregulation of GFAP. Among 1101 genes related to cellular regulatory mechanisms, the expression of two genes, both for insulin-like growth factors, (IGF-1) and ErbB3, was altered upon administration of the alpha/beta-blockers, the alpha1-blocker, and the alpha2-agonist.


CONCLUSIONS
Our present study suggests that modulations of the alpha-adrenergic receptor, alpha1-blocking and alpha2-stimulation, by antiglaucoma eye drops may cause beneficial effects on NMDA-induced retinal damage in the rat.
Metoki
Tomomi
T
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan.
Ohguro
Hiroshi
H
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan. ooguro@cc.hirosaki-u.ac.jp.
Ohguro
Ikuyo
I
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan.
Mamiya
Kazuhisa
K
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan.
Ito
Tadashi
T
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan.
Nakazawa
Mitsuru
M
Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan.
D018674:Adrenergic Antagonists / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D016202:N-Methylaspartate / Q000633:toxicity; D009883:Ophthalmic Solutions; D012313:RNA / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012164:Retinal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
D018674:Adrenergic Antagonists; D000959:Antihypertensive Agents; D005904:Glial Fibrillary Acidic Protein; D009883:Ophthalmic Solutions; D012313:RNA; D016202:N-Methylaspartate