title: Pharmacologic synergism of ocular ketorolac and systemic caffeine citrate in rat oxygen-induced retinopathy.
abstract: Caffeine or ketorolac decrease the risk of retinopathy of prematurity and may act synergistically to improve beneficial effect. Combination of caffeine (Caff) and ketorolac (Keto) to prevent oxygen-induced retinopathy was studied.
  
  
  
  Newborn rats exposed to room air (RA) or intermittent hypoxia (IH) consisting of 12% O2 during hyperoxia (50% O2) from birth (P0) had single daily IP injections of Caff from P0-P13 or saline; and/or ocular Keto (Acuvail, 0.45% ophthalmic solution) administered subcutaneously over the eyes from P5-P7. Pups were studied at P14 or placed in RA for recovery from IH (IHR) until P21. Eyes were examined for neovascularization, histopathology, growth factors, and VEGF-signaling genes.
  
  
  
  Severe retinal damage noted during IHR in the untreated groups evidenced by hemorrhage, neovascularization, and oxygen-induced retinopathy (OIR) pathologies were prevented with Keto/Caff treatment. Keto and/or Caff treatment in IH also promoted retinal neural development evidenced by eye opening (92%, P < 0.001 vs. 31% in the placebo-treated IH group). No corneal pathologies were noted with Keto.
  
  
  
  Caff or Keto given individually reduced retinal neovascularization, but the two drugs given together prevented severe OIR.
authors.affiliation: Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York.|Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn, New York.|State University of New York Eye Institute, New York, New York.
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Aranda
authors.affiliation: Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York.
authors.forename: Taimur
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York.
authors.forename: Vadim
authors.initials: V
authors.lastname: Bronshtein
authors.affiliation: Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sadeh
authors.affiliation: Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York.
authors.forename: Gloria B
authors.initials: GB
authors.lastname: Valencia
authors.affiliation: Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn, New York.|State University of New York Eye Institute, New York, New York.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lazzaro
authors.affiliation: Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, New York.|Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn, New York.|State University of New York Eye Institute, New York, New York.
authors.forename: Kay D
authors.initials: KD
authors.lastname: Beharry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001081:Apyrase / Q000378:metabolism; D001158:Arteries / Q000378:metabolism; D001835:Body Weight; D002110:Caffeine / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D002829:Choroid / Q000378:metabolism; D002951:Citrates / Q000008:administration & dosage*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D006470:Hemorrhage; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020910:Ketorolac / Q000008:administration & dosage*; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000188:drug therapy*; D015398:Signal Transduction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000697:Central Nervous System Stimulants; D002951:Citrates; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; C548904:insulin-like growth factor-1, rat; C075750:8-epi-prostaglandin F2alpha; D002110:Caffeine; D007334:Insulin-Like Growth Factor I; D015237:Dinoprost; D040281:Vascular Endothelial Growth Factor Receptor-1; D001081:Apyrase; D010100:Oxygen; C026189:caffeine citrate; D020910:Ketorolac