Spare the rod and spoil the eye

Br J Ophthalmol. 2005 Jun;89(6):764-9. doi: 10.1136/bjo.2004.062547.


This review presents a new unified view of the pathogenesis of three common causes of acquired retinal degenerative disease-diabetic retinopathy, age related macular degeneration, and retinopathy of prematurity. In these three conditions, angiogenesis has a predominant role in the development of sight threatening pathology. Angiogenesis is controlled by among other factors the expression of vascular endothelial growth factor (VEGF), which in turn is regulated by absolute and relative lack of oxygen. The severe pathological manifestations of these three conditions are not part of a general underlying disease process because they are peculiar to the eye, and the profound hypoxia that develops in normal retina during dark adaptation (rod driven hypoxia) is an adequate and elegant additional factor to explain their pathogenesis. A large number of experimental reports support this conclusion, although rod driven anoxia is not generally considered as a causal factor in ocular disease. However, the hypothesis can be critically tested, and also suggests novel methods of treatment and prevention of these conditions that may be simpler and more inexpensive than current therapies and that have a smaller potential for adverse effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Hypoxia
  • Cytokines / biosynthesis
  • Dark Adaptation
  • Diabetic Retinopathy
  • Humans
  • Infant, Newborn
  • Macular Degeneration / etiology
  • Macular Degeneration / physiopathology
  • Retinal Diseases / etiology
  • Retinal Diseases / physiopathology*
  • Retinal Neovascularization / etiology
  • Retinal Neovascularization / physiopathology
  • Retinal Rod Photoreceptor Cells / physiology*
  • Retinopathy of Prematurity / etiology
  • Retinopathy of Prematurity / physiopathology
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism


  • Cytokines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A