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Impressum
INS37217, a P2Y2 receptor agonist, increases subretinal fluid reabsorption in pig models of small and large bullous retinal detachments
1,3Meyer C. H., 1Oliveira L. B., 2Peterson W. M., 1Toth C. A.
1Department of Ophthalmology, Duke University Medical Center, Durham, NC; 2Inspire Pharmaceuticals, Inc., Durham, NC; 3Universitätsaugenklinik, Phillips-Universität, Marburg
Purpose: INS37217, a synthetic P2Y2 receptor agonist, enhances
the reabsorption rate of subretinal fluid under specific physiologic conditions
in rabbits, presumably by stimulating the RPE pump function.This has previously
been demonstrated by us in small, experimentally-induced subretinal blebs.
The present study is designed to evaluate the potential clinical benefit
of INS37217 on subretinal fluid reabsorption under normal surgical conditions
in large experimental retinal detachments in pigs.
Methods: In the first series of experiments, approximately 5 µl
BSS+ was injected subretinally into both eyes, followed by a masked intravitreal
BSS+ injection (50 µl) with or without INS37217 (~12 mM) in 10 pigs
(aged 3 - 10 weeks). Subretinal fluid reabsorption was observed over 5
hours using indirect ophthalmoscopy. In a second series of experiments,
a central vitrectomy and a large retinal detachment extending 1-2 quadrants
(300 µl of BSS+ injected subretinally) was performed in one eye
in each of 12 pigs. Either BSS+ without or with INS37217 (5.6 mM) was
injected into the midvitreous cavity and observed over 3 -7 days by indirect
ophthalmoscopy, ultrasound and OCT-imaging.
Results: In both series of experiments, enhanced reabsorption of
subretinal fluid was observed in eyes treated with INS37217 when compared
with eyes treated with vehicle. In the second series of experiments, complete
reabsorption of subretinal fluid in the large retinal detachments was
observed within 36 hours in all eyes treated with INS37217, and after
5-7 days in all control eyes.
Conclusion: Intravitreal application of INS37217 enhanced the reabsorption
rate of subretinal fluid in experimental animal models of small and large
retinal detachments. INS37217 may therefore be useful as a surgical adjunct
to stimulate subretinal fluid reabsorption in retinal detachment or in
limited macular translocation surgery in humans.