ABSTRACT
The pharmacologic activity phase assessed the action of a single dose of INS37217 intravitreal injection versus placebo during the first 24 hours after dosing. INS37217 is a synthetic dinucleotide that is engineered with improved metabolic stability when compared with Adenosine triphosphate (ATP) and uridine 5'-triphosphate (UTP). The effects of INS37217 on recovery of electroretinography function were evaluated in the mouse following experimental retinal detachment and spontaneous reattachment. The ability to reattach the retina in the treatment of retinal detachment is contingent on removing the pathological accumulation of subretinal fluid between the retina and the underlying retinal pigment epithelium (RPF). One such cell-surface receptor is the G protein-coupled P2Y2 receptor, which is normally activated by extracellular ATP and UTP and functionally expressed at the RPE apical membrane. From a drug delivery perspective, localization of P2Y2 receptors at the RPE apical membrane requires that INS37217 must be present in the subretinal space to bind to the target receptor.
