Purinergic Receptors in Ocular Inflammation

Abstract

Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A), and P1,P5-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl)-5′-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

“…Thus, a common pathogenic growth factor-κB-TNF-α (NF-kB-TNF-α) signaling pathway, the inhibition of cytokines secretion, and the apoptosis of inflammatory cells [73]. It has been suggested that the improvement of several pathological signs and symptoms in subjects with DE, such as Schirmer test and BUT scores, might be due to reduced ocular surface's inflammation following direct interaction between CF101 and its receptors on inflammatory cells [73].…”

“…An equilibrate balance between ω3 and ω6 is necessary to avoid the prevalence of ω6 proinflammatory effect. In particular, proresolving lipid mediators derived from ω-3 precursors, such as docosahexaenoic acid (DHA) and eicopentaenoic acid (EPA), control epithelial wound healing, inflammatory cell migration, and nerve regeneration [74,75] subsequent generation of eicosanoid lipid mediators is responsible to trigger the acute inflammatory response to corneal injury [73]. But, its resolution is mediated by proresolving lipid mediators derived from ω-3 PUFA precursors, DHA and EPA.…”

Ocular Purine Receptors as Drug Targets in the Eye

“…P2X2R is present in the trigeminal ganglion sensory neurons and ciliary body. 112 In chronic glaucoma, ATP is released through pannexin hemichannels in astrocytes of the optic nerve and activates P2X7Rs that can increase cell death in the retina. The ATP release from astrocytes can result from chronic mechanical strain (stretch) as it occurs in glaucoma through the upregulation of pannexins.…”

Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the Eye

“…20,21,72,73 The purinergic system is fully represented in this part of the eye since apart from the presence of these receptors, the existence of enzymes responsible for the degradation of nucleotides, a nucleotide vesicular transporter, has also been detected. 74 Altogether nucleotides and dinucleotides may play important roles acting in the retina as autocrine and paracrine mediators.…”