The Role of the P2X7 Receptor in Ocular Stresses: A Potential Therapeutic Target

Abstract

Abstract:The P2X7 receptor is expressed in both anterior and posterior segments of the eyeball. In the ocular surface, the P2X7 receptor is activated in case of external aggressions: preservatives and surfactants induce the activation of P2X7 receptors, leading to either apoptosis, inflammation, or cell proliferation. In the retina, the key endogenous actors of age-related macular degeneration, diabetic retinopathy, and glaucoma act through P2X7 receptors' activation and/or upregulation of P2X7 receptors' expression. Different therapeutic strategies aimed at the P2X7 receptor exist. P2X7 receptor antagonists, such as divalent cations and Brilliant Blue G (BBG) could be used to target either the ocular surface or the retina, as long as polyunsaturated fatty acids may exert their effects through the disruption of plasma membrane lipid rafts or saffron that reduces the response evoked by P2X7 receptor stimulation. Treatments against P2X7 receptor activation are proposed by using either eye drops or food supplements.

Neuroprotective Factors of the Retina and Their Role in Promoting Survival of Retinal Ganglion Cells: A Review

“…Another method of modulating CNTF expression is through the inhibition of the purinergic receptor P2X7 (P2X7R) [43]. The P2X7R is an ionotropic receptor activated by extracellular adenosine triphosphate, which promotes the synthesis of various pro-inflammatory mediators that support neuroinflammation which later leads to neurodegeneration.…”

“…The P2X7R can be found on microg-lial cells, astrocytes, and neurons throughout the central nervous system including the retina, and also in other structures of the globe such as the cornea, lens cells, etc. [43,44]. Antagonizing P2X7R weakens the inflammatory response and leads to neuroprotection [43,[45][46][47].…”

“…[43,44]. Antagonizing P2X7R weakens the inflammatory response and leads to neuroprotection [43,[45][46][47]. Recently, it was shown that chronic application of eye drops containing P2XR7 antagonist in mice with glaucoma decreased the number of activated microglia and prevented the loss of RGCs [46].…”

The Role of Purinergic Receptors in the Circadian System

“…In the absence of extracellular ATP, P2X7 receptors expressed on macrophages can act as scavenger receptors that play an important role in the innate immune system [68]. There is increasing evidence that P2X7 receptor function contributes to retinal pathologies such as glaucoma [69][70][71], inherited retinal degenerations, as well as inflammatory changes associated with AMD [72] and diabetic retinopathy (reviewed in [68]). However, little is known about the interaction of the circadian clock and/or melatonin and the purinergic system in retinal physiology and pathology.…”

Special Issue for Purinergic Receptors, Particularly P2X7 Receptor, in the Eye

“…Dutot et al [22] summarize the role of the P2X 7 receptor in exogenous and endogenous ocular stresses as well as in ocular diseases including AMD, diabetic retinopathy, and glaucoma. Treatments to inhibit P2X 7 receptor activation are proposed, using either eye-drops or food supplements.…”