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

Diadenosine tetraphosphate abbreviated Ap₄A is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of Ap₄A are mostly carried out by P2Y₂ receptors, but the participation of P2X2 and P2Y₆ in processes such as the regulation of intraocular pressure (IOP), together with the P2Y₂, is pivotal. Beyond the physiological role, this dinucleotide can present on the ocular surface keeping a right production of tear secretion or regulating IOP. It is important to note that exogenous application of Ap₄A to cells or animal models can significantly modify pathophysiological conditions and thus is an attractive therapeutic molecule. The ocular location where Ap₄A actions have not been fully elucidated is in the retina. Although some analogues show interesting actions on pathological situations such as retinal detachment, little is known about the real effect of this dinucleotide, this being one of the challenges that require pursuing in the near future.