title: Subchoroidal Release of VEGF and bFGF Produces Choroidal Neovascularization in Rabbit.
abstract: Intravitreal vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) produced florid retinal neovascularization and hemorrhage in the rabbit. This study seeks to determine whether sustained subchoroidal release of both VEGF and bFGF can induce robust choroidal neovascularization (CNV) in the rabbit.
  
  
  
  Subchoroidal implantation through the sclera of polymeric pellets containing both 15 μg VEGF and 15 μg bFGF was performed on adult pigmented male Dutch belted rabbits (N = 6) and NZW albinos (N = 8). As negative controls, blank pellets with no growth factors were implanted in both Dutch belted rabbits (N = 6) and NZW albino rabbits (N = 4). Development of CNV was documented weekly over a 4-week period with indirect ophthalmoscopy, color fundus photography, and fluorescein angiography. Eyes were enucleated and prepared for histologic and immunohistochemical analyses at the end of the study. Amounts of VEGF and bFGF that were released in vitro from the pellets were measured by ELISA.
  
  
  
  In all eyes with subchoroidal implants containing both VEGF and bFGF, strong fluorescein leakage was observed at 2, 3, and 4 weeks (P < 0.005); no leakage was seen initially in week 1. Negative control groups with blank implants showed no fluorescein leakage throughout the 4-week study period. Histologic analysis confirmed the presence of experimental CNV. New subretinal blood vessel growth occurred in all eyes with VEGF/bFGF implants. Negative control eyes with blank implants showed no vascular changes. In vitro sustained release of both VEGF and bFGF was confirmed by ELISA.
  
  
  
  Sustained subchoroidal release of both VEGF and bFGF produced experimental CNV rapidly in the rabbit. Understanding how these growth factors induce CNV may suggest novel therapeutic strategies in the large rabbit eye.
authors.affiliation: a SCLERA LLC , Carlsbad , CA , USA.
authors.forename: Corinne G
authors.initials: CG
authors.lastname: Wong
authors.affiliation: b Department of Ophthalmology , College of Medicine, University of California Irvine , Irvine , CA , USA.
authors.forename: Mehran
authors.initials: M
authors.lastname: Taban
authors.affiliation: c Department of Medicine , College of Medicine, University of California Irvine , Irvine , CA , USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Osann
authors.affiliation: d Doheny Eye Institute , Los Angeles , CA , USA.
authors.forename: Fred N
authors.initials: FN
authors.lastname: Ross-Cisneros
authors.affiliation: e University of California Los Angeles , Los Angeles , CA , USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Bruice
authors.affiliation: f Consulting , Berlin , Germany.
authors.forename: Grit
authors.initials: G
authors.lastname: Zahn
authors.affiliation: g Orange County Retina Group , Santa Ana , CA , USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: You
mesh_terms: D000818:Animals; D002829:Choroid / Q000378:metabolism* / Q000473:pathology; D020256:Choroidal Neovascularization / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008297:Male; D009887:Ophthalmoscopy; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D004343:Drug Implants; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2
keywords: Basic fibroblast growth factor; robust rabbit CNV model; subchoroidal sustained release; transscleral implantation; vascular endothelial growth factor