Purchase this article with an account.
Xianmin Luo, George N. Lambrou, José A. Sahel, David Hicks; Hypoglycemia Induces General Neuronal Death, Whereas Hypoxia and Glutamate Transport Blockade Lead to Selective Retinal Ganglion Cell Death In Vitro. Invest. Ophthalmol. Vis. Sci. 2001;42(11):2695-2705.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. To examine the impact of experimental ischemia and interruption of
glutamate transport on retinal neuronal cell, especially retinal
ganglion cell (RGC), survival in vitro.
methods. Cell cultures were prepared from adult pig retinas and maintained under
different experimental conditions of increasing hypoglycemia,
environmental hypoxia (delayed postmortem period or atmospheric
PO2 <2%), or chemical hypoxia (potassium cyanide), or in
the presence of glutamate transporter blockers l-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) and l(−)-threo-3-hydroxyaspartic acid (THA), or the glutamine
synthetase inhibitor methionine sulfoximine (MS). After 48 hours, cells
were returned to standard culture conditions and allowed to develop for
5 days, when they were fixed and immunostained with different retinal
neuronal phenotypic markers.
results. Control normoxic cultures contained large numbers of
immunocytochemically identified photoreceptors (PRs), bipolar cells
(BCs), amacrine cells (ACs), and RGCs after 7 days in vitro. A 24-hour
postmortem delay before culture led to significant reductions in all
types (40%–70%), proportionately greater in ACs and RGCs. Lowering
of sugar levels also led to increased losses in all cell types, whereas
potassium cyanide treatment deleteriously affected only ACs and RGCs.
Ambient hypoxia led to consistent reductions only in the number of
RGCs, which were exacerbated by addition of high concentrations of
glutamate. Inclusion of glutamate receptor antagonists had a partial
protective effect against RGC loss. Treatment with tPDC and THA also
led to selective RGC death, but MS had no effect on any cells.
conclusions. Different components of the ischemic pathologic process (hypoxia,
hypoglycemia, glutamate transport failure) lead to distinctly different
patterns of neuronal loss in adult retina in vitro. RGCs are especially
vulnerable, corresponding to their in vivo susceptibility. These data
may suggest neuroprotective strategies for limiting retinal damage
This PDF is available to Subscribers Only