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Atsushi Kawasaki, Yasumasa Otori, Colin J. Barnstable; Müller Cell Protection of Rat Retinal Ganglion Cells from Glutamate and Nitric Oxide Neurotoxicity. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3444-3450.
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purpose. Low concentrations of excitotoxic agents such as glutamate and nitric
oxide decrease survival rates of purified retinal ganglion cells
(RGCs). In the retina, RGCs are ensheathed by retinal Müller
glial (RMG) cell processes. The purpose of this study was to determine
whether RMG cells could protect RGCs from these excitotoxic injuries.
methods. RGCs were purified from 7- or 8-day-old Long Evans rats and cultured on
polylysine/laminin-coated coverslips in serum-free medium for 2 days.
The coverslips were then moved to dishes containing either confluent
RMG monolayers or no glial cells in glutamate-free medium. Some dishes
with confluent RMG cells were exposed to d,l-threo-β-hydroxyaspartate (THA), a blocker of
glutamate uptake. Three days after exposure to various concentrations
of glutamate or the NO donor,
2,2′-(hydroxynitroso-hydrazino)bisethanamine, survival rates of RGCs
were measured by calcein-acetoxymethyl ester staining. Glutamate
concentrations in the medium were measured using amino acid analysis.
results. Without RMG cells, the application of increasing concentrations (5–500μ
M) of glutamate caused a dose-dependent increase in RGC death after
3 days. The neurotoxic effects of glutamate were blocked in the RMG
cell cocultures, even when there was no direct contact between the cell
types. The protective effect of RMG cells was weakened by THA
treatment. NO also had toxic effects on RGC. RMG cells prevented this
toxicity but only when in direct contact with the RGCs.
conclusions. RMG cells can protect RGCs from glutamate and NO neurotoxicity. We
suggest that functional disorders of glutamate uptake in RMGs might be
one of the etiologies of glaucoma.
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