Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease that afflicts as much as 60% of all extremely low gestational age neonates (ELGANs, <1250g/<28 weeks) with approximately 5% condemned to a lifetime of blindness. Caffeine and NSAIDs have already been shown to decrease the risk of severe ROP in ELGANs. We propose a novel approach of combining topical ketorolac or systemic ibuprofen with systemic caffeine to optimize their efficacy for prevention of ROP. The overarching goal of this proposal is to investigate the synergistic effects of NSAIDs potentiated with systemic caffeine on the incidence and severity of ROP.
Our specific aims are three-fold: 1) To establish the synergistic effect of local ophthalmic NSIADs and systemic caffeine as optimal therapies for the attenuation and/or prevention of severe ROP. We hypothesize that ocular ketotolac or systemic ibuprofen potentiated with systemic caffeine will prevent or diminish the severity of ROP;2) To identify a """"""""critical"""""""" number of arterial oxygen desaturations as a key risk factor for severe ROP. We hypothesize that there is a """"""""critical"""""""" number of daily arterial oxygen desaturations experienced by ELGANs during the first two weeks of life that is a key risk factor for severe ROP;and 3) To determine whether infants at risk for severe ROP are haploinsufficient for the delta-like ligand 4 (D114). We hypothesize that ELGANs at risk for severe ROP will have different pattern of gene expression specifically related to the Notch signaling pathway, as has been previously shown in animal models. We will use gene profiling to determine whether haploinsufficiency of DII4 is associated with severe ROP. We will use state-of-the-art technologies to provide insights on the biomolecular mechanisms associated with ROP. We have all the necessary technologies and systems in order to successful accomplish these proposed works.

Public Health Relevance

The unique strategy proposed in these studies is the use of topical ketorolac or systemic ibuprofen complemented with systemic caffeine citrate to prevent ROP in ELGANs. The impact of these studies will be substantial, including the prevention of a long life of blindness, and minimizing the economic burden for the care of growing blind children. ROP is the leading cause of childhood blindness and the epidemic is increasing. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to evaluate the molecular mechanisms that regulate progression of the disease. Here we provide an improved, unique and alternate approach that is safer, and less invasive.

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-DSR-A)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Suny Downstate Medical Center
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