GROWTH FACTORS IN OXYGEN INJURED NEONATAL EYES

Project: Research project

Project Details

Description

DESCRIPTION The neonatal eye continues to be at high risk for injury as a result of premature birth and exposure to high levels of oxygen, often developing retinopathy of prematurity (ROP). The neovascularization that is characteristic of ROP is result of a pathologic process superimposed upon a complex developmental sequence. Recent studies suggest that growth factors contribute to this pathologic process. The overall objective of this research project is to elucidate the role of polypeptide growth factors in hyperoxic-induced injury in the neonatal eye. There are two phases observed in ROP, a period of vaso-obliteration and subsequent vasoproliferation. As a mechanism of hyperoxia-induced vaso-obliteration, it is hyppthesized that endothelial cell death occurs as a result of apoptosis. When the injured retina is returned to room air it will become hypoxic as a result of the vaso-obliteration. The ischemic retina responds with pathologic neovascularization. Furthermore, it is hypothesized that multiple growth factors are critical during both phases of ROP, vasoproliferation and vaso-obliteration. The first step to test these hypothesis is to define, expand, and confirm the list of growth factors that play a role in the pathogenesis of ROP. The applicant will determine if specific growth factors (acidic fibroblast growth factor, aFGF; basic FGF, bFGF; transforming growth factor-alpha, TGF-alpha; and TGF-beta) are altered during specific phases of ROP using a mouse model of ROP. The second step is test of the role of specific growth factors through unique genetically-altered mice. The studies will determine if specific growth factors (aFGF, bFGF, TGF-alpha) are critical or merely bystanders during the evolution of ROP. These studies will also help define the complexities of growth factor interactions in the pathogenesis of ROP. The third step will be to examine the role apoptosis has in the pathogenesis of ROP. He will define the temporal and cellular pattern of apoptosis in the hyperoxic-injured retina and then manipulate the apoptotic process through the use of genetically-altered mice, TNF-alpha receptor-deficient mice and Fas-ligand mutant mice. These studies will help define mechanistic pathways of apoptotic cell death in hyperoxic-injured retinal cells.
StatusFinished
Effective start/end date4/1/988/31/13

Funding

  • National Institutes of Health: $385,000.00
  • National Institutes of Health
  • National Institutes of Health: $293,087.00
  • National Institutes of Health: $104,300.00
  • National Institutes of Health: $298,906.00
  • National Institutes of Health: $104,300.00
  • National Institutes of Health: $104,300.00
  • National Institutes of Health: $306,667.00
  • National Institutes of Health
  • National Institutes of Health: $299,068.00

ASJC

  • Medicine(all)

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