Maekawa Tomoki, PhD, DDS; Anna Tan Cheng Sim, MBBS; Ricardo A. Pena-Silva, PhD
Competition Sponsor: Japan Agency for Medical Research and Development
Ageing has contradictory effects on calcium metabolism, causing bone demineralization (osteoporosis) while in blood vessels and soft tissues proinflammatory cytokines activate osteogenesis and biomineralization, resulting in ectopic calcification. Aging is also associated with decreased expression of modulators of inflammation and osteogenesis such as DEL-1 (developmental endothelial locus-1). Ectopic calcification is seen in age-related macular degeneration, a major cause of blindness. Similarly, age-related calcification of coronary and carotid arteries, and heart valves, is major cause of morbidity due to stroke, heart and renal failure. Collectively, these diseases affect up to 9% of the elderly and induce an enormous burden of disease, increasing health care costs worldwide. In vivo non-invasive retinal imaging enables identification of biomarkers of age-related pathological calcification. If noninvasive retinal imaging of calcification in the ageing retina and cardiovascular calcification can be correlated, retinal examination has the potential to detect age-related ectopic calcification and monitor its progression.
We hypothesize that A) retinal imaging can be used to monitor ectopic calcification in the ageing cardiovascular systems, and B) DEL-1 can downregulate proinflammatory, profibrotic and osteogenic processes associated with age-related ectopic calcification.
Our preliminary findings suggest a good correlation between the formation of calcifying nodules in cultures of vascular smooth muscle cells (VSMC) and retinal pigmented epithelial cells (RPEC) in response to aging and inflammation. We also found that recombinant DEL-1 decreases calcification in vitro. Our multidisciplinary team intends to use retinal imaging to identify biomarkers of ectopic calcification, which could be useful for the screening of early stages of disease in at-risk populations. Additionally, we intend to study recombinant DEL-1, and inducers of DEL-1 (erythromycin), as novel therapeutic targets for ectopic calcification, not only in the retinal and cardiovascular systems, but also in other inflammatory and metabolic disorders, associated with ageing.