title: Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration.
abstract: Recent studies have shown that the retinal blood vessels are damaged in experimental models of retinal degeneration, but the mechanisms underlying their damage are not fully understood. In this study, we examined the possible role of transforming growth factor (TGF)-β in retinal neuron loss and capillary degeneration induced in rats by an intravitreal injection of N-methyl-d-aspartate (NMDA). The number of cells in the ganglion cell layer was significantly decreased 2 days after NMDA treatment, and a further decrease was observed at 7 days. Enhanced capillary degeneration was detected 7 days after NMDA treatment. Simultaneous injection of NMDA and the TGF-β inhibitor (SB431542 or LY364947) slightly but significantly attenuated the reduction in number of cells in the ganglion cell layer and almost completely prevented the enhancement of capillary degeneration. These results suggest that activation of the TGF-β signaling pathway induces neuronal and vascular cell damage in rat retina.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ueda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D004149:Dioxoles / Q000494:pharmacology*; D004195:Disease Models, Animal; D058449:Intravitreal Injections; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D011720:Pyrazoles / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D012164:Retinal Diseases / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011804:Quinolines
chemical_list: D001549:Benzamides; D004149:Dioxoles; D016202:N-Methylaspartate; D011720:Pyrazoles; D011758:Pyrroles; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C506615:HTS 466284; D011804:Quinolines