Introduction 1 Fig. 1 − Ado  Purines and subretinal space RPE-photoreceptor interactions across the subretinal space 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Purinergic receptors on photoreceptors 2 18 2 2+ 19 20 2 21 2A 22 2 23 2 24 7 25 Purinergic receptors on the RPE 2 26 27 2A 28 2 29 - 30 2+ 31 2+ 1 2A 32 33 1 2A 34 1 2A 1 2 35 37 38 2 31 1 2 4 6 39 1 12 40 41 32 33 42 43 2 2 2+ - + 43 2 2 44 45 46 2 47 2 Regulation of purine levels in subretinal space While synthesized purinergic agonists may prove useful in treating some ocular disorders, the endogenous activation of P1 and P2 receptors in the subretinal microenvironment will ultimately be determined by availability of agonists. These levels are largely controlled by the release of ATP into the subretinal space, its conversion into other purines including adenosine, and the manipulation of adenosine by enzymes or transporters. Recent work has increased our understanding of both the stimuli that initiate changes in subretinal purine levels and the mechanisms that mediate these changes. Release of ATP by the RPE 39 40 48 51 51 52 2+ 2+ 51 40 48 - 2 53 54 55 2 56 57 Fig. 2 51 Left Right n n p  172 50 cftr -/- mice 58 43 2+ 50 2+ 48 2+ 51 59 Interconversion of purines in subretinal space The interconversion of nucleotides and nucleosides each capable of stimulating distinct receptors makes the purinergic signaling system of particular interest in a confined region such as the subretinal space. The main enzymes responsible for dephosphorylating extracellular ATP on the RPE cells have been analyzed and a basic understanding of their regulation has begun. This section first describes the enzymes that act on ATP and ADP, followed by enzymes which convert AMP into adenosine. 40 60 61 40 62 63 63 64 65 63 63 16 29 Physiologic effects of subretinal purines on the RPE and photoreceptors 25 2A