title: Changes in glutamate homeostasis cause retinal degeneration in Royal College of Surgeons rats.
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.
authors.affiliation: Southwest Eye Hospital, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhengqin
authors.initials: Z
authors.lastname: Yin
authors.forename: Chuanhuang
authors.initials: C
authors.lastname: Weng
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D003720:Densitometry; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012162:Retinal Degeneration / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D012333:RNA, Messenger; C493466:Slc17a7 protein, rat; C493392:Slc1a3 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D018698:Glutamic Acid; D051571:Protein Kinase C-alpha; D005974:Glutamate-Ammonia Ligase