Sabiha Hacibekiroglu, graduate student - (shacibek<at>gmail.com)
My project combines cell and gene therapy to treat and cure age-related macular degeneration (AMD) and diabetic retinopathy (DR). AMD and DR are both eye diseases that can lead to visual impairment and loss. The cause for this is abnormal and leaky blood vessel growth that affects the macula, the part of the retina that is responsible for central vision. Overexpression of VEGF leads to choroidal neovascularization, vascular leakage, vessel dilatation, tortuosity and haemorrhage. Current treatments include injection of anti-angiogenics such as anti-VEGF-A antibody (e.g. Bevazizumab). Such treatments improve visual function due to regression of neovascular AMD and abnormal blood vessels. However, these treatments require monthly or bi-monthly injections due to its transient effect, and cause side effects such as hypertension, congestive heart failure and bleeding. The aim of this study is to generate biologics with locally acting anti-VEGF activity for minimally invasive and controlled long-term administration. We generated VEGF sticky-traps by modifying the original VEGF trap. This modification maintains the ability to trap VEGF as well as bind (i.e. "stick") to the ECM through binding to heparan-sulphate proteoglycans. This consequently allows inhibition of angiogenesis only at the site of expression or administration. Here, we aim to generate retina pigment epithelium (RPE) cells from human iPS cells that express VEGF sticky-traps in an inducible manner. We hypothesize that injection of these cells into the eye will allow for long term control expression and treatment of AMD and DR.