Metabolomic changes underpinning the development of sub-retinal pigment epithelial deposits in macular degeneration and Alzheimer's disease.

Therefore, I investigated calcium-phosphate mineral deposition in an animal model in which a loss of function mutation had been introduced for a protein that is involved in mineralisation. The mutations in Enpp1 lead to a calcification phenotype in the eye and this animal model can now be used to study calcification further.<br><br>I was also involved in the characterisation of eyes from human PXE sufferers, and we were able to show for the first time that Bruch’s membrane calcification is more complex than originally predicted to be.

With the characterisation of calcification models as well as human tissues, I also investigated commercially available and novel calcium phosphate-specific fluorescent dyes. With these, I demonstrated the potential to use fluorescence-based sensors for earlier disease detection as a principium.<br><br>Detection of metabolic changes has the potential to help with disease identification and monitoring also. I developed an analysis pipeline for metabolomics using tear fluid.

This pipeline was used to identify changes in tear composition following zinc supplementation. As zinc dysregulation plays a role in AMD, and disease progression can be slowed by nutritional supplementation of zinc, this approach can now be applied to uncovering the metabolic changes associated with calcification. <br><br>During this PhD I was able to establish that mineralisation in the back of the eye has a multitude of effects and further work will be needed to fully understand the metabolic changes associated with blinding diseases like AMD and PXE.<br><br><i>Thesis is embargoed until 31 December 2028.</i>