Purchase this article with an account.
Po-shan Margaret Luke, Terry LeVatte, David Clarke; Absence of Neural Cell Adhesion Molecule (NCAM) influences injured retinal cell survival. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1774.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The low affinity neurotrophin receptor p75 (p75NTR) is known to control retinal cell death caused by intense light illumination. Recently, we found that high levels of p75NTR were expressed in young adult retinas in the absence of NCAM, which is not only involved in cell migration, axonal fasciculation, neurite outgrowth and formation of synapses during development, but is also necessary for normal adult retinal ganglion cell number and survival. Using light-induced injury to the retina as a model, we sought to investigate whether high levels of p75NTR in NCAM -/- mice are associated with an alteration in retinal cell survival.
2 months old, dark-adapted wild-type (WT) and NCAM -/- mice in a C57Bl/6 background (n=12/ group) were anaesthetized and, with dilated pupils, exposed to 12,000 lux of white fluorescent light for 6 hours. Animals were sacrificed at several time intervals, from 0 to 4 days after light induction. Expression levels of active caspase 3, p75NTR and actin were measured by immunoblot, and apoptotic cell death was assessed by TUNEL assay.
Exposure to excessive light results in retinal cell death, which is known to induce the caspase- dependent apoptosis pathway. In WT mice, levels of caspase 3 activation were detected at low levels on the first day, followed by an increase up to 4 days after light induced retinal damage. Similar results were obtained with the rate of apoptosis. In contrast, in NCAM -/- mice, higher baseline cleaved caspase 3 levels were found earlier at Day 0 and Day 1, followed by reduced levels by Day 4. These results indicate that higher levels of p75NTR in NCAM -/- mice may induce earlier onset of retinal cell death.
In the absence of NCAM, elevated levels of p75NTR are expressed in the retina. The earlier cell death in these animals after light-induced injury demonstrates that NCAM plays an important role in determining the survival of these injured retinal cells.
This PDF is available to Subscribers Only