Dual Roles of Diadenosine Polyphosphates in Corneal Epithelial Cell Migration

Abstract

Based on the pharmacological profile of all the compounds tested, the two main P2Y receptors that exist in these corneal cells are a P2Y(2) receptor accelerating the rate of healing and a P2Y6 receptor that delays this process.

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

“…Experiments performed in our laboratory on an animal model, demonstrated that the levels of Ap 4 A and Ap 5 A are significantly reduced after the damage, recovering after 10 h. The same ratio of Ap 4 A/Ap 5 A concentration in tears remained stable. This means that diadenosine polyphosphates remain low during the latency phase and recover during the migration phase, suggesting their involvement in the migration process (Mediero et al, 2006).…”

“…The expression of P2 receptors in different ocular surface locations suggests the involvement of these receptors in the physiology of the eye (Guzman-Aranguez and . In fact, during the last decade, the role of several nucleotides and their receptors in ocular processes, including tear secretion (through P2Y 2 receptor) (Jumblatt and Jumblatt, 1998;Murakami et al, 2000), corneal wound healing (P2Y 2 is able to accelerate the corneal re-epithelization and proliferation, meanwhile P2Y 6 inhibits the process) (Byun et al, 2016;Crooke et al, 2009;Mediero et al, 2006), and corneal epithelial migration and stromal organization (mediated through P2X7 receptor) have been described (Mankus et al, 2012;Mayo et al, 2008).…”

“…Mechanical perturbations such as cell stretching (Patel et al, 2005), hydrostatic pressure (Cockayne et al, 2000;Ferguson et al, 1997;Knight and Burnstock, 2001) and compressive stress (Sauer et al, 2000) seem to be the candidates to trigger the release of these dinucleotides. The motion of the upper eyelid during the blinking process seems to be responsible for exerting shear stress on the epithelial cells and therefore increasing the levels of both diadenosine polyphosphates, concomitantly with the increase in the blinking frequency Rat, mouse and human Epithelial migration and stroma reorganization (Dutot et al, 2008;Groschel-Stewart et al, 1999;Mayo et al, 2008) P2Y 1 , P2Y 4 Rabbit, rat and human Undetermined (Klepeis et al, 2004;Pintor et al, 2004b) P2Y 2 Monkey, rabbit, rat and human Re-epithelization, corneal proliferation and corneal permeability increasing (Cowlen et al, 2003;Crooke et al, 2009;Klepeis et al, 2004;Loma et al, 2015b;Mediero et al, 2008;Pintor et al, 2004b) P2Y 6 Rabbit, rat and human Re-epithelization delay and corneal proliferation increasing (Klepeis et al, 2004;Mediero et al, 2006;Pintor et al, 2004b) P2Y 11 Rabbit and human Undetermined (Klepeis et al, 2004) Conjuctival Epithelium P2X7 Human Membrane permeabilization associated with iatrogenic pathology (Dutot et al, 2008) P2Y 2 Monkey, dog, rabbit and human Tear fluid and mucin secretion stimulation (Cowlen et al, 2003;Jumblatt and Jumblatt, 1998;Li et al, 2001;Murakami et al, 2000;Terakado et al, 2014) Rat and monkey Undetermined (Cowlen et al, 2003;Tanioka et al, 2014) described above were collected in subjects from 18 to 38 years old (Pintor et al, 2002a). The age is considere...…”

“…In contrast, Ap 5 A has the opposite effect, inhibiting the cell migration (Crooke et al, 2009;Mediero et al, 2009Mediero et al, , 2008Mediero et al, , 2006. So, the high concentration of Ap 4 A on the day after LASIK and PRK surgery could be used to accelerate the wound healing process.…”

“…It means that only diadenosine tetraphosphate provokes an increase in the wound healing rate (Pintor et al, 2004a). Based on these results, Mediero et al evaluated the role of diadenosine polyphosphate in the epithelial cell migration, performed in primary corneal epithelial cell culture (Mediero et al, 2006). Ap 4 A accelerate 5 h the wound healing whereas Ap 3 A and Ap 5 A delayed it 6.5 h and 10 h respectively.…”