Living patient-derived mini-tissues as a novel tool to understand and treat children and adolescent myopia

Myopia is a growing public health challenge. More than 2 billion people worldwide are myopic, 15% of whom have the severe potentially blinding form of myopia. Myopia prevalence and severity are increasing rapidly, and by 2050, more than half of the world population may be affected, placing an enormous burden on health services to manage myopia and prevent vision loss from blinding complications. Myopia develops almost exclusively during eye growth in childhood/adolescence, after which the changes to the eye shape and structure, and subsequent vision alteration, become irreversible or worsen. Myopia is genetically heterogenous, with over 400 associated genetic loci affecting multiple anatomical components of the eye. Environmental factors are also critical in myopia onset and progression, with lack of outdoor activity, early education and increasingly urban lifestyles being key. Yet, to date, the mechanisms by which myopia develops and progresses, and the role of specific genes, remain unclear, thwarting efficient prevention and treatment. We propose a completely new approach to understanding human eye growth and myopia, combining tissue engineering, gene expression profiling, stem cell technology and genetics to understand the interactions between three layers critical for eye growth: the sclera, choroid and retinal pigment epithelium (RPE). We will use donor sclera and choroid fibroblasts and matching induced pluripotent stem cell (IPSC)-derived RPE cells to engineer complex age-specific organoids, to understand changes linked to normal eye growth and maturation, and investigate directly for the first time the role of myopia candidate genes and/or study patients’ own mutations.