Retinal angiogenesis is evident in a number of different pathological and
degenerative conditions including proliferative diabetic retinopathy, retinopathy of
prematurity and age-related macular degeneration. There have been numerous attempts
to control retinal angiogenesis but the fragility of the tissue and the presence of the
blood retinal barrier limiting the transport of pharmacological agents has proved
problematic in the therapeutic regulation of this process. This chapter presents the
structure of the retina in relation to the structure of the eye. In addition, the molecular
initiators of angiogenesis are discussed and in particular how the hyperglycaemic
environment leads to oxidative stress in proliferative diabetic retinopathy. The lack of
perfusion due to damage from the diabetic milieu, the impaired retinal development in
the case of retinopathy of prematurity and the aging of the retinal pigment epithelial
cells are characteristics that are associated with angiogenesis. The consequent reduction
in oxygen level that follows impaired perfusion creates an hypoxic environment that
stabilises hypoxia inducible factor type 1 alpha and precipitates the activation of
hypoxia inducible factor type 1. The activation of this transcription factor leads to the
increased expression of a number of genes including vascular endothelial growth factor
and this is central to the angiogenic process. The development of specific
pharmacological inhibitors of aldose reductase, protein kinase Cβ, advanced glycatedend
products, hypoxia inducible factor type 1 alpha and vascular endothelial growth
factor are reviewed. Inhibition using small interfering RNAs to inhibit specific
pathways and the use of cell replacement is discussed in terms of their therapeutic
potential.
Keywords: Age-related macular degeneration, Angiogenesis, Diabetes, Diabetic
retinopathy, Reactive oxygen species, Retina, Retinopathy of prematurity.
