title: Triamcinolone reduces neovascularization, capillary density and IGF-1 receptor phosphorylation in a model of oxygen-induced retinopathy.
abstract: OBJECTIVE
  To study the effects of intravitreous triamcinolone acetonide (TA) on neovascularization (NV), capillary density, and retinal endothelial cell (REC) viability in a model of oxygen-induced retinopathy (OIR).
  
  
  METHODS
  Newborn rats exposed to OIR underwent intravitreous injections (right eye) at day 14 to achieve intravitreous concentrations of: dexamethasone (DEX) (0.3 mg/mL), triamcinolone (TA; 0.4-4 mg/mL), or PBS. Animals were removed to room air and at day 18, retinal flatmounts were assayed for clock hours of NV, percent peripheral avascular retina, capillary density, apoptosis, and VEGF protein. At day 15, retinas were assayed for insulin-like growth factor (IGF)-1 receptor phosphorylation (IGF-1Rphos). Human RECs exposed to TA were assayed for trypan blue exclusion or activated caspase-3.
  
  
  RESULTS
  TA but not DEX or PBS reduced NV (ANOVA, P < 0.001), capillary density (ANOVA, P < 0.001), and systemic weight gain (ANOVA, P = 0.002). VEGF protein was not different between TA- and PBS-injected or noninjected groups. Apoptosis was not increased in vivo or in vitro between groups, but there was a dose-dependent toxic effect of TA on cultured RECs (P < 0.001). At day 15, retinas from the 4 mg/mL TA-injected OIR group had a trend toward reduced IGF-1Rphos compared with room air-raised PBS- or non-injected OIR groups.
  
  
  CONCLUSIONS
  TA caused dose-dependent reductions in NV, retinal vascularization, and systemic weight gain associated with a reduction in IGF-1Rphos. Long-term studies are needed to assess TA toxicity in vivo. TA doses should be carefully considered before administering the drug in diseases with ongoing retinal vascular development, such as retinopathy of prematurity.
authors.affiliation: Department of Ophthalmology, University of North Carolina, 6109A Neuroscience Research Building, Chapel Hill, NC 27599, USA. hartnet@med.unc.edu
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Hartnett
authors.forename: David J
authors.initials: DJ
authors.lastname: Martiniuk
authors.forename: Yuta
authors.initials: Y
authors.lastname: Saito
authors.forename: Pete
authors.initials: P
authors.lastname: Geisen
authors.forename: Lynda J
authors.initials: LJ
authors.lastname: Peterson
authors.forename: Janet R
authors.initials: JR
authors.lastname: McColm
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002196:Capillaries; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000473:pathology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007267:Injections; D010100:Oxygen / Q000633:toxicity; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects*; D012178:Retinopathy of Prematurity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body
chemical_list: D005938:Glucocorticoids; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003907:Dexamethasone; D017526:Receptor, IGF Type 1; D014222:Triamcinolone Acetonide; D010100:Oxygen