4.7 Article

Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 699, Issue 1-3, Pages 188-193

Publisher

ELSEVIER
DOI: 10.1016/j.ejphar.2012.11.054

Keywords

Endothelial cell; Excitotoxicity; Retinal degeneration; Retinal blood vessel; Transforming growth factor-beta

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [23122517, 20590090, 23590112]
  2. Grants-in-Aid for Scientific Research [24590329, 20590090, 23122517, 23590112] Funding Source: KAKEN

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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)-beta 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-beta 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-beta signaling pathway induces neuronal and vascular cell damage in rat retina. (C) 2012 Elsevier B.V. All rights reserved.

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