Sustained elevation of extracellular ATP in aqueous humor from humans with primary chronic angle-closure glaucoma

Abstract

While the death of retinal ganglion cells in glaucoma is frequently associated with an elevation of intraocular pressure (IOP), the mechanisms connecting the two processes remain unclear. Extracellular ATP is released throughout the body in response to mechanical deformations. We have previously shown that patients with an acute rise in IOP have an elevated concentration of ATP in the anterior chamber. In the present study we ask whether ATP levels remain increased in patients with chronic elevations of IOP. The concentration of ATP in samples of aqueous humor obtained from patients with primary chronic angle-closure glaucoma (PCACG) was compared with that from control cataract patients whose IOP was normal. The mean ATP concentration in aqueous humor was 14-fold higher for PCACG samples than for control. ATP levels were correlated with IOP and the cup-to-disk ratio (C/D ratio). Brief treatment of Timolol, Alphagan, Pilocarpine and/or Azopt did not affect the rise in ATP concentration. In conclusion, sustained elevations in extracellular ATP levels accompany the chronic elevation of IOP in chronic glaucoma. As numerous ocular tissues express purinergic receptors, an increased extracellular ATP may have diverse physiological and pathophysiological effects.