Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy?

Steven Pennock, Luis J. Haddock, Dean Eliott, Shizuo Mukai, Andrius Kazlauskas

Research output: Contribution to journalReview article

71 Scopus citations

Abstract

Proliferative vitreoretinopathy (PVR) is a blinding disorder that occurs in eyes with rhegmatogenous retinal detachment and in eyes that have recently undergone retinal detachment surgery. There are presently no treatment strategies to reduce the risk of developing PVR in eyes with retinal detachment, and surgical intervention is the only option for eyes with retinal detachment and established PVR. Given the poor visual outcome associated with the surgical treatment of PVR, considerable work has been done to identify pharmacologic agents that could antagonize the PVR process. Intensive efforts to identify molecular determinants of PVR implicate vitreal growth factors. A surprise that emerged in the course of testing the 'growth factor hypothesis' of PVR was the existence of a functional relationship amongst growth factors that engage platelet-derived growth factor (PDGF) receptor α (PDGFRα), a receptor tyrosine kinase that is key to pathogenesis of experimental PVR. Vascular endothelial cell growth factor A (VEGF), which is best known for its ability to activate VEGF receptors (VEGFRs) and induce permeability and/or angiogenesis, enables activation of PDGFRα by a wide spectrum of vitreal growth factors outside of the PDGF family (non-PDGFs) in a way that triggers signaling events that potently enhance the viability of cells displaced into vitreous. Targeting these growth factors or signaling events effectively neutralizes the bioactivity of PVR vitreous and prevents PVR in a number of preclinical models. In this review, we discuss recent conceptual advances in understanding the role of growth factors in PVR, and consider the tangible treatment strategies for clinical application.

Original languageEnglish (US)
Pages (from-to)16-34
Number of pages19
JournalProgress in Retinal and Eye Research
Volume40
DOIs
StatePublished - May 2014
Externally publishedYes

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Keywords

  • Growth factors
  • PDGFR
  • Proliferative vitreoretinopathy
  • Retinal detachment
  • Signaling
  • Vitreous

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

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