A continuum mathematical model of the developing murine retinal vasculature

Bull Math Biol. 2011 Oct;73(10):2430-51. doi: 10.1007/s11538-011-9631-y. Epub 2011 Feb 1.

Abstract

Angiogenesis, the process of new vessel growth from pre-existing vasculature, is crucial in many biological situations such as wound healing and embryogenesis. Angiogenesis is also a key regulator of pathogenesis in many clinically important disease processes, for instance, solid tumour progression and ocular diseases. Over the past 10-20 years, tumour-induced angiogenesis has received a lot of attention in the mathematical modelling community and there have also been some attempts to model angiogenesis during wound healing. However, there has been little modelling work of vascular growth during normal development. In this paper, we describe an in silico representation of the developing retinal vasculature in the mouse, using continuum mathematical models consisting of systems of partial differential equations. The equations describe the migratory response of cells to growth factor gradients, the evolution of the capillary blood vessel density, and of the growth factor concentration. Our approach is closely coupled to an associated experimental programme to parameterise our model effectively and the simulations provide an excellent correlation with in vivo experimental data. Future work and development of this model will enable us to elucidate the impact of molecular cues upon vasculature development and the implications for eye diseases such as diabetic retinopathy and neonatal retinopathy of prematurity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / physiology
  • Cell Movement
  • Endothelial Cells / physiology
  • Mathematical Concepts
  • Mice
  • Models, Biological
  • Neovascularization, Physiologic
  • Platelet-Derived Growth Factor / physiology
  • Retinal Vessels / cytology
  • Retinal Vessels / embryology
  • Retinal Vessels / growth & development*
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Platelet-Derived Growth Factor
  • Vascular Endothelial Growth Factor A
  • platelet-derived growth factor A
  • vascular endothelial growth factor A, mouse