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Editors Selection IGR 11-4

Basic research: Serum-deprivation

Comment by Jonathan Crowston on:

11715 Serum deprivation induces apoptotic cell death of transformed rat retinal ganglion cells via mitochondrial signaling pathways, Charles I; Khalyfa A; Kumar DM et al., Investigative Ophthalmology and Visual Science, 2005; 46: 1330-1338

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Serum-deprivation is well recognized as a model for studying apoptosis in different cell types, yet the underlying mechanisms responsible for the induction of apoptosis are less well characterized. Charles et al. (81) report that serum withdrawal induced rapid and extensive apoptosis in a transformed retinal ganglion cell line (RGC-5). Characterization of the apoptotic pathways showed that serum deprived cells undergo mitochondrion-directed apoptosis associated with the loss of mitochondrial membrane potential, caspase activation and an increase in proapoptotic gene expression with elevated Bax/ Bcl-2 ratios. In addition there was pertubation of the oxidative state with increased malonyldialdehyde and reduced glutathione levels in cell lysates. The authors speculate that apoptosis from serum withdrawal may mimic retinal ganglion cell apoptosis in glaucoma, which is thought to be due to the blockade of axonal retrograde transport of neurotrophins. As stated by the authors, further work is clearly required to determine whether this is in fact the case. Unlike primary retinal ganglion cells, the transformed RGC-5 cells are able to proliferate and it is also possible that the apoptosis machinery is altered in the transformation process. In addition, it is necessary to determine the components of serum that are required to maintain RGC survival. These may not be limited to neurotrophic growth factors as other components such as albumin, which is plentiful in serum, have been shown to inhibit serum-deprivation induced apoptosis. This manuscript elicits the apoptotic pathways that mediate apoptosis due to serum withdrawal in a transformed retinal ganglion cell line. Whether this does indeed provide a useful model for studying retinal ganglion cell apoptosis in glaucoma remains to be determined.

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