Impairment of neuronal glutamate uptake and modulation of the glutamate transporter GLT-1 induced by retinal ischemia.
Excitotoxicity has been implicated in the retinal neuronal loss in several ocular pathologies including glaucoma. Dysfunction of Excitatory Amino Acid Transporters is often a key component of the cascade leading to excitotoxic cell death. In the retina, glutamate transport is mainly operated by the glial glutamate transporter GLAST and the neuronal transporter GLT-1. In this study we evaluated the expression of GLAST and GLT-1 in a rat model of acute glaucoma based on the transient increase of intraocular pressure (IOP) and characterized by high glutamate levels during the reperfusion that follows the ischemic event associated with raised IOP. No changes were reported in GLAST expression while, at neuronal level, a reduction of glutamate uptake and of transporter reversal-mediated glutamate release was observed in isolated retinal synaptosomes. This was accompanied by modulation of GLT-1 expression leading to the reduction of the canonical 65 kDa form and upregulation of a GLT-1-related 38 kDa protein. These results support a role for neuronal transporters in glutamate accumulation observed in the retina following an ischemic event and suggest the presence of a GLT-1 neuronal new alternative splice variant, induced in response to the detrimental stimulus.
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, Italy. rossella.russo@unical.it
Rossella
R
Russo
Federica
F
Cavaliere
Giuseppe Pasquale
GP
Varano
Marco
M
Milanese
Annagrazia
A
Adornetto
Carlo
C
Nucci
Giambattista
G
Bonanno
Luigi Antonio
LA
Morrone
Maria Tiziana
MT
Corasaniti
Giacinto
G
Bagetta
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001692:Biological Transport; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000378:metabolism*; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism*; D007429:Intraocular Pressure; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D013574:Synaptosomes / Q000378:metabolism
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C493392:Slc1a3 protein, rat; D001224:Aspartic Acid; D018698:Glutamic Acid