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Editors Selection IGR 17-4

Basic research: Oxidative stress

Comment by Keith Martin on:

20092 Oxidative stress is an early event in hydrostatic pressure induced retinal ganglion cell damage, Liu Q; Ju WK; Crowston JG et al., Investigative Ophthalmology and Visual Science, 2007; 48: 4580-4589

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The mechanisms by which retinal ganglion cells (RGC) die in glaucoma remain a hot topic for investigation. Given that all cells in the retina are exposed to elevated intraocular pressure (IOP) in glaucoma, it is of particular interest why RGC are especially vulnerable to pressure-induced apoptosis and how the damaging effects of pressure are mediated. In a well-designed and executed series of experiments, Liu et al. (1235) examine the effect of elevated pressure on markers of oxidative stress in cultured RGC-5 cells and in the retinas of mice exposed to experimental ocular hypertension. In contrast to many previous studies, care was taken to ensure that pH, pCO₂ and pO₂ were unaffected by pressure elevation in the culture system. The authors found that significant oxidative stress occurs within hours of elevated hydrostatic pressure in culture or elevated IOP.

The authors are realistic about the limitations of using RGC-5 cells as a surrogate for the behaviour of RGC in vivo. RGC-5 is a transformed cell line that proliferates in culture and lacks ion channels characteristic of RGC in the adult retina. Also, RGC-5 cells do not develop extended axons and therefore the contribution of axonal injury to RGC death in glaucoma cannot be investigated in this system. Nevertheless, the results in culture hint at a direct effect of hydrostatic pressure on cells and it would be interesting to know if other neuronal cell lines are more resistant and, if so, why. Also, the fact that similar results were found in the animal model is important and the results have potential clinical relevance as evidence of early oxidative stress in glaucoma might strengthen the case for investigating the adjunctive use of anti-oxidants to treat the condition. Further studies of oxidative changes in glaucoma are awaited with great interest.

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