Abstract
The corneal endothelium is the innermost layer of the human cornea, the eye's transparent window. A dysfunctional endothelium leads to corneal opacification, which is a common cause of corneal blindness worldwide and results in an unavoidable need for a transplantation. Unfortunately, the global donor shortage causes very long waiting lists. A pharmacological compound to stimulate in vivo corneal endothelial regeneration therefore is a very interesting alternative treatment to reduce the reliance on donor corneas. However, there are many limitations regarding the traditional drug discovery pipelines such as high cost and long development times. Moreover, the corneal anatomy hampers drug permeation. The aim of my PhD therefore is to tackle both these limitations so to deliver an innovative pharmacological treatment. Hence, this project proposes a high throughput biological screening of repurposed drugs, i.e. the screening of formerly approved compounds. This biological data will serve to develop and train a virtual compound screening model to predict additional potential lead compounds. The high throughput screenings together with a thorough characterization and optimalization of the physico-chemical properties of the main hits, will lead to the identification of one repurposed lead compound. Eventually, I will assemble this compound together with a corneal permeability enhancer into an inventive eye drop that facilitates corneal penetration to reach the endothelium.
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