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X. Zhang, D. Reigada, M. Zhang, A.M. Laties, C.H. Mitchell; Increased Ocular Pressure Increases Vitreal Levels of ATP . Invest. Ophthalmol. Vis. Sci. 2006;47(13):426.
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Mechanical perturbations such as increased pressure trigger a physiologic release of ATP from many tissues. Glaucoma is typically characterized by elevated intraocular pressure, with visual loss due to the loss of retinal ganglion cells. As these ganglion cells can be killed by the stimulation of P2X7 receptors for ATP, the effect of elevated pressure on retinal ATP release was investigated.
Bovine eyecups bisected at the ora serrata with vitreous humor replaced with buffer were placed in a small chamber maintained at various pressures. The ATP released from the retina into the vitreal chamber was determined with the luciferase assay.
Elevating pressure by only 20 mm Hg doubled the ATP levels in the buffer. Increasing pressure further by 50, 70 and 100 mm Hg led to a proportional increase in ATP. The rise in ATP levels was sustained at higher pressures, but transient at 20 and 50 mm Hg. The elevation in ATP was not accompanied by an increase in lactose dehydrogenase, implying the ATP arose from physiological release and not cell damage. This release was blocked by NPPB, consistent with release from a Cl– channel. Increasing pressure with either N2 or air led to similar levels of ATP release, implying changes in partial pressure did not contribute.
Moderate elevations of ocular pressure trigger a physiologic release of ATP into the extracellular space surrounding retinal cells. If a similar release is triggered by the increased pressure of glaucoma, the excess ATP could act at P2X7 receptors and kill ganglion cells.
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