Increased angiogenic factors associated with peripheral avascular retina and intravitreous neovascularization: a model of retinopathy of prematurity

Arch Ophthalmol. 2010 May;128(5):589-95. doi: 10.1001/archophthalmol.2010.65.

Abstract

Objectives: To determine expression of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor, and their respective receptors in retinas using a model of retinopathy of prematurity.

Methods: Retinas isolated from a 50/10 oxygen (inspired oxygen cycled between 50% oxygen and 10% oxygen every 24 hours)-induced rat model of retinopathy of prematurity (50/10 OIR model), and from room air-raised rat pups (RA) at birth, age 14 days (persistent peripheral avascular retina in the 50/10 OIR model and complete retinal vascularization in RA) and age 18 days (intravitreous neovascularization in the 50/10 OIR model) were analyzed for messenger RNA of VEGF(164), neuropilin 1, neuropilin 2, VEGF receptor 1, VEGF receptor 2, pigment epithelium-derived factor, and pigment epithelium-derived factor receptor by real-time polymerase chain reaction.

Results: In the 50/10 OIR model compared with RA, fold changes in expression of VEGF(164), neuropilin 1, and neuropilin 2 were significantly increased at ages 14 and 18 days. A trend for increased fold change was noted in expression of VEGF receptor 2 at age 14 days and a significant increase at age 18 days in the 50/10 OIR model compared with RA. Pigment epithelium-derived factor receptor was significantly increased at age 14 days in the 50/10 OIR model compared with RA.

Conclusion: Increased expression of VEGF(164) and angiogenic receptors were found in association with both avascular retina at day 14 and intravitreous neovascularization at day 18 in a relevant model of retinopathy of prematurity.

Clinical relevance: Increased VEGF and angiogenic receptors may have a role in the development of peripheral avascular retina and stage 3 retinopathy of prematurity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Disease Models, Animal*
  • Eye Proteins / genetics*
  • Gene Expression Regulation / physiology*
  • Humans
  • Infant, Newborn
  • Nerve Growth Factors / genetics*
  • Neuropilin-1 / genetics
  • Neuropilin-2 / genetics
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide / genetics*
  • Retinal Neovascularization / genetics*
  • Retinopathy of Prematurity / classification
  • Retinopathy of Prematurity / genetics*
  • Serpins / genetics*
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Vitreous Body / blood supply

Substances

  • Eye Proteins
  • Nerve Growth Factors
  • Neuropilin-2
  • RNA, Messenger
  • Receptors, Neuropeptide
  • Serpins
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor
  • pigment epithelium-derived factor receptor
  • vascular endothelial growth factor A, rat
  • Neuropilin-1
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2