Hormonal Therapeutic for Retinopathy of Prematurity

Whenever premature birth interrupts normal retinal vascularization of the developing eye retinopathy of prematurity ROP can occur When ROP was first reported in the s it was associated with high oxygen delivery to preterm infants Though oxygen delivery to preterm infants is now carefully regulated ROP is still a common occurrence In very low birthweight infants birth weights andlt g ROP incidence exceeds Despite treatment for advanced disease ROP is a leading cause of visual disability in the U S and abroad The current understanding of ROP is that ROP initiates due to a delay in retinal vascularization which leads to retinal ischemia and ultimately to advanced vasoproliferative disease Though photocoagulation and vitrectomy are used to treat late stage ROP there is a high unmet need for preventative agents An important mission of Zietchick Research Institute LLC ZRI is to develop new therapeutics for maternal child eye health In this Phase I SBIR grant project ZRI will establish proof of principle that a hormone enriched therapeutic for premature infants can serve as a game changing strategy for ROP prevention In this proposal ZRI will first present strong preliminary data that two related hormones human chorionic gonadotropin hCG and luteinizing hormone LH influence retinal vessel formation ZRI will next present two research aims For Aim I ZRI will quantify levels of hCG and LH on stored biosamples from human preterm infants to show that these hormone levels are significantly lower in ROP cases compared to controls For Aim ZRI will demonstrate that neonatal mice who lack hCG LH receptors have abnormal retinal vascularization resembling human ROP Successful completion of these two aims will allow ZRI to proceed to Phase II to develop a hormone based therapeutic for pre clinical testing which will ultimately reduce the burden of pediatric blindness all over the world Retinopathy of prematurity ROP diagnosed in of very low birth weight VLBW infants birth weights andlt g is a disorder of abnormal retinal development It is a leading cause of pediatric visual disability in the U S and abroad Though there are some options for late stage disease there are currently no therapeutics for ROP prevention Our SBIR PHASE I is based on a proposed pathway to ROP involving two reproductive hormones and their novel role in ocular development We will examine hormone levels in VLBW infants with and without ROP to show that certain hormones levels are lower in those infants with ROP We will also show the abnormal retinal vascularization occurs in mice who lack specific hormone receptors Accomplishment of our aims will establish proof of concept that a hormone based supplement for preterm infants may represent a game changing strategy for ROP prevention