The purpose of the present experiments was to evaluate
the contribution of the glutamate-glutamine cycle in retinal
glial (Müller) cells to photoreceptor cell synaptic
transmission. Dark-adapted isolated rat retinas were superfused
with oxygenated bicarbonate-buffered media. Recordings
were made of the b-wave of the electroretinogram
as a measure of light-induced photoreceptor to ON-bipolar
neuron transmission. L-methionine sulfoximine (1–10
mM) was added to superfusion media to inhibit glutamine
synthetase, a Müller cell specific enzyme, by more
than 99% within 5–10 min, thereby disrupting the
conversion of glutamate to glutamine in the Müller
cells. Threo-hydroxyaspartic acid and D-aspartate were
used to block glutamate transporters. The amplitude of
the b-wave was well maintained for 1–2 h
provided 0.25 mM glutamate or 0.25 mM glutamine was included
in the media. Without exogenous glutamate or glutamine
the amplitude of the b-wave declined by about
70% within 1 h. Inhibition of glutamate transporters led
to a rapid (2–5 min) reversible loss of the b-wave
in the presence and absence of the amino acids. In contrast,
inhibition of glutamine synthetase did not alter significantly
either the amplitude of the b-wave in the presence
of glutamate or glutamine or the rate of decline of the
b-wave found in the absence of these amino acids.
Excellent recovery of the b-wave was found when
0.25 mM glutamate was resupplied to L-methionine sulfoximine–treated
retinas. The results suggest that in the isolated rat retina
uptake of released glutamate into photoreceptors plays
a more important role in transmitter recycling than does
uptake of glutamate into Müller cells and its subsequent
conversion to glutamine.
Effect of diabetes blood-stasis syndrome and Xuefu Zhuyu decoction on ROS-ERK1/2 signaling pathway in rat retina Müller cells
