Retinopathy of prematurity (ROP) occurs in 50 to 80% of preterm babies born weighing less than 1250 grams. The NYPD-PRC (New York Pediatric Developmental Pharmacology Research Consortium) was formed as a unique multidisciplinary research team of neonatal pharmacologist, retina investigators, neonatologists and pharmaceutical scientists to define the molecular events leading to ROP and to develop effective and safe pharmacologic strategies to prevent it. The overarching hypothesis is that repeated hyperoxic/hypoxic episodes promoting aberrant ocular VEGF signaling, dysregulated angiogenesis and vasoproliferation can be modulated or prevented by synergistic interventions of caffeine and systemic ibuprofen or ocular NSAID local drops. Using novel intervention strategies and unique approaches, three distinct but highly inter-related study proposals will test various hypotheses and specific aims in newborn rats, retinal endothelial tip cell cultures and in preterm newborn infants born <28 weeks or weighing <1250 grams. Protocol 1 will determine the efficacy and safety of ocular ibuprofen or ketorolac with systemic caffeine as well as the critical timing of intervention for the prevention of oxygen induced retinopathy in newborn rat model of OIR. Protocol II will examine the behavior of retinal endothelial tip cells and their dynamic relationship with astrocytes in the setting of oxidative stress (hyperoxia/hypoxia cycling);and to determine whether ibuprofen co-administered with caffeine will preserve tip cell quiescence. Once studies on additional safety, efficacy and critical timing of intervention (vasoobliterative or vaso-proliferative phase) are completed, Protocol III will be implemented in preterm newborns weighing <1250 grams, to test the safety, efficacy, pharmacodynamics and pharmacogenomics of systemic caffeine with or without IV ibuprofen or with or without local NSAID eye drops (ketorolac) in a multicenter, randomized, open label study to prevent ROP (all stages). Unique pharmacometric analyses of all 3 protocols provide novel data on ocular drug transport and action during development. The NYPD-PRC will surely elevate the level of scientific inquiry on molecular and clinical pharmacology of ROP to hasten its prevention and avert life-long blindness.

Public Health Relevance

Retinopathy of Prematurity or ROP occurs in 2 out of 3 small babies born prematurely and treated with oxygen. ROP is the most common cause of blindness in children. Understanding the molecular events leading to ROP and providing novel, effective and safe drug interventions will avert a lifetime of blindness, disability and darkness.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Zajicek, Anne
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Suny Downstate Medical Center
Schools of Medicine
United States
Zip Code
Beharry, Kay D; Cai, Charles L; Henry, Michael M et al. (2017) Co-Enzyme Q10 and n-3 Polyunsaturated Fatty Acid Supplementation Reverse Intermittent Hypoxia-Induced Growth Restriction and Improved Antioxidant Profiles in Neonatal Rats. Antioxidants (Basel) 6:
Vali, Payam; Chandrasekharan, Praveen; Rawat, Munmun et al. (2017) Evaluation of Timing and Route of Epinephrine in a Neonatal Model of Asphyxial Arrest. J Am Heart Assoc 6:
Tu, Chengjian; Shen, Shichen; Sheng, Quanhu et al. (2017) A peptide-retrieval strategy enables significant improvement of quantitative performance without compromising confidence of identification. J Proteomics 152:276-282
Tu, Chengjian; Mojica, Wilfrido; Straubinger, Robert M et al. (2017) Quantitative proteomic profiling of paired cancerous and normal colon epithelial cells isolated freshly from colorectal cancer patients. Proteomics Clin Appl 11:
Tan, Jeffrey J; Cai, Charles L; Shrier, Eric M et al. (2017) Ocular Adverse Effects of Intravitreal Bevacizumab Are Potentiated by Intermittent Hypoxia in a Rat Model of Oxygen-Induced Retinopathy. J Ophthalmol 2017:4353129
Beharry, Kay D; Cai, Charles L; Valencia, Gloria B et al. (2017) Human retinal endothelial cells and astrocytes cultured on 3-D scaffolds for ocular drug discovery and development. Prostaglandins Other Lipid Mediat :
Tu, Chengjian; Li, Jun; Shen, Shichen et al. (2016) Performance Investigation of Proteomic Identification by HCD/CID Fragmentations in Combination with High/Low-Resolution Detectors on a Tribrid, High-Field Orbitrap Instrument. PLoS One 11:e0160160
Beharry, Kay D; Valencia, Gloria B; Lazzaro, Douglas R et al. (2016) Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity. Semin Perinatol 40:189-202
Tu, Chengjian; Bu, Yahao; Vujcic, Marija et al. (2016) Ion Current-Based Proteomic Profiling for Understanding the Inhibitory Effect of Tumor Necrosis Factor Alpha on Myogenic Differentiation. J Proteome Res 15:3147-57
Shen, Shichen; Jiang, Xiaosheng; Li, Jun et al. (2016) Large-Scale, Ion-Current-Based Proteomic Investigation of the Rat Striatal Proteome in a Model of Short- and Long-Term Cocaine Withdrawal. J Proteome Res 15:1702-16

Showing the most recent 10 out of 40 publications