INVESTIGATION OF THE LINK BETWEEN CHOROIDAL THICKNESS CHANGES AND RETINAL HYPOXIA-INDUCED FACTOR-ALPHA PATHWAY
The project aims to clarify the possible role of the retinal HIF-1α signalling pathway on normal growth, and on the inhibitory (stimulated by plus lens wear) and stimulatory (stimulated by minus lens wear and deprivation) eye growth and how they interact with dopaminergic signalling and choroidal thickness changes in the animal model of the chick. A possible influence of reduced oxygenation on myopia development is supported by genetic studies in mice and humans, which linked a number of genes involved in the development of refractive errors to the cellular response to hypoxia. Photoreceptors, because of their high metabolism and constant renewal of the outer segment, are particularly sensitive to oxygen deficits and their oxygen and nutrition supply is exclusively mediated by the choroid. Hypoxia-inducible factor-alpha subunits (HIF-αs) are the major transcription factors that mediate a response to hypoxia. By using a pharmacological approach, DC9 will assess the link between choroidal thickness, retinal HIF-1α signalling and eye growth. DS9 will study both the effects that occur within a few hours of treatment and the effects after long-lasting treatment. The latter needs to be studied intensively since most treatment paradigms for myopia inhibition in children (pharmacologic, optically) apparently lose their effect over time, but information about feedback-control and adaption to treatment are not available currently.  The doctoral candidate will use non-invasive optical measuring techniques and biochemical and molecular genetics research methods.