Changes in glutamate homeostasis cause retinal degeneration in Royal College of Surgeons rats

Int J Mol Med. 2013 May;31(5):1075-80. doi: 10.3892/ijmm.2013.1297. Epub 2013 Mar 12.

Abstract

The aim of the present study was to investigate glutamate homeostasis in retinal degeneration-induced changes and the potential mechanisms of glutamate-mediated excitotoxicity in a rat model. The expression of vesicular glutamate transporter-1 (VGLUT-1) and protein kinase Cα (PKCα) in wild-type and Royal College of Surgeons (RCS) rat retinas, at postnatal Day 15 (P15), P30, P60 and P90, were detected using quantitative real-time polymerase chain reaction and immunohistochemistry. The levels of glutamine synthetase (GS) and L-glutamate/L-aspartate transporter (GLAST) were evaluated by western blotting. Compared with wild-type rats, outer nuclear layer thickness was significantly thinner and VGLUT-1 expression was upregulated in a time-dependent pattern in RCS rats. The ratio of VGLUT-1 to PKCα in RCS rats peaked at P60 (p<0.01) and subsequently decreased by P90 (p<0.01), while it remained constant in wild-type rats. The expression of GS increased gradually from P30 to P90 in RCS rats (p<0.01), while it remained constant in wild-type rats at various time-points. No significant difference in GLAST expression was found between RCS and wild-type rats at all stages of retinal degeneration. Our results confirm the occurrence of glutamate-mediated excitotoxicity to RCS rat retinas and provide an experimental foundation for safeguarding the remnant visual function in retinal degenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Blotting, Western
  • Densitometry
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Fluorescent Antibody Technique
  • Glutamate-Ammonia Ligase / metabolism
  • Glutamic Acid / metabolism*
  • Homeostasis*
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Retinal Degeneration / enzymology
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology*
  • Vesicular Glutamate Transport Protein 1 / genetics
  • Vesicular Glutamate Transport Protein 1 / metabolism

Substances

  • Excitatory Amino Acid Transporter 1
  • RNA, Messenger
  • Slc17a7 protein, rat
  • Slc1a3 protein, rat
  • Vesicular Glutamate Transport Protein 1
  • Glutamic Acid
  • Protein Kinase C-alpha
  • Glutamate-Ammonia Ligase