Cellular and molecular mechanisms of human choroidal and retinal vascularisation

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The abnormal growth of new blood vessels is a major cause of blindness in people of all ages. In premature infants, changes in retinal blood vessels results in Retinopathy of Prematurity (ROP) the leading cause of infant blindness in the world. In older adults with age-related macular degeneration (ARMD), vessels in the choroid can grow into and under the retina where they can cause catastrophic loss of vision. This association of abnormal vessel growth with the most common causes of blindness has motivated the search for a better understanding of how blood vessel growth in the eye is controlled in healthy tissues and how these controls fail in disease. Our proposal addresses this issue directly. Recent work shows that this neovascularization is not only a response to a rise in the local concentration of molecules that induce such angiogenesis, but also requires a fall in the levels of endogenous molecules that inhibit angiogenesis. Our study will investigate the expression of newly identified angiogenic growth factors (VEGFs) and their receptors as well as angiogenic inhibitors (VEGI and PEDF) in the developing and adult human retina and choroid. We will examine the mechanisms by which the human choroid is formed. Our preliminary results suggests the novel insight that vasculogenesis (the formation of blood vessels via transformation of vascular precursor cells) plays a major role the formation of both the human retina and choroid. Further, these exciting results suggest involvement of novel growth stimulators and inhibitors previously not known to play a role in these processes. Our studies will lead to new insights regarding the vascular growth factors and inhibitors that drive this process, thus leading to a rational basis for new therapeutic targets for the treatment of ARMD. The rapid aging of the Australian population and the consequent predicted doubling of ARMD incidence in the next 20 years demonstrates the urgency of our studies.