Disease relevance of

• Effect of INS37217, a P2Y(2) receptor agonist, on experimental retinal detachment and electroretinogram in adult rabbits [1].
• These results support the use of INS37217 to help restore function after therapies that involve subretinal administration of drugs in animal models of retinal diseases [2].
• CONCLUSIONS: These results demonstrate that INS37217 enhances subretinal fluid reabsorption in experimental retinal detachment in rabbits and support the development of INS37217 for stimulating subretinal fluid reabsorption in conditions that result in retinal detachment or retinal edema [1].
• Subretinal injections of 1 micro L of fluorescent microbeads, saline, or INS37217 (1-200 micro M) were made by the transvitreal method in normal (C57BL/6) mice and in mice heterozygous for the retinal degeneration slow (rds) gene [2].
• The enhanced metabolic stability and resultant increased duration of improved mucociliary clearance may confer significant advantages to INS37217 over other P2Y(2) agonists in the treatment of diseases such as cystic fibrosis [3].

High impact information on

• Phase II clinical trials have recently shown that aerosolized denufosol (INS37217, Inspire(R)) improves pulmonary function in CF patients: denufosol was granted orphan drug status and phase III trials are planned [4].
• To evaluate the effects of INS37217 on the recovery of retinal function after experimental retinal detachment induced by subretinal injection [2].
• P2Y(2) receptor agonist INS37217 enhances functional recovery after detachment caused by subretinal injection in normal and rds mice [2].
• Additionally, INS37217 reduced the number of TUNEL-positive photoreceptors and the enhanced rate of reattachment [2].
• Enhancement of ERG recovery by INS37217 is likely due to reduced retinal folding and cell death associated with detachment [2].

Biological context of

• PURPOSE: To investigate the effects of INS37217, a synthetic P2Y(2) receptor agonist, on intracellular calcium signaling, electrophysiology, and fluid transport in vitro and on experimentally induced retinal detachment in rat eyes in vivo [5].
• Most recently, INS37217, a metabolically stable and potent P2Y(2) agonist has been developed and studies have shown it to be well-tolerated when given via inhalation [6].

Anatomical context of

• This extended duration of action is consistent with the ability of INS37217 to resist metabolism by airway cells and sputum enzymes [3].

Gene context of

• Clinical trials are under way to test the effect of synthetic purinergic compounds, such as the P2Y(2) receptor agonist INS37217, on the progression of lung disease in patients with CF [7].
• The P2Y(2) receptor agonist INS37217 stimulates RPE fluid transport in vitro and retinal reattachment in rat [5].
• Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis [8].

References