Generation and Neuroprotective Studies of NF1 Patient-derived RGCs

Neurofibromatosis type 1 (NF1) is the most common genetic condition in which individuals carrying the mutation are predisposed to develop different types of tumors. Approximately 20% of children with NF1 mutations will develop tumors of the nerve that carries visual information from the eye to the brain, so called optic pathway gliomas (OPGs). NF1-OPGs can cause permanent vision loss ranging from a mild decline in visual acuity to complete blindness.

Vision loss from NF1-OPGs ultimately results from damage to and loss of the retinal ganglion cells (RGCs), the retinal neurons that carry visual information from the eye to the brain. Since mammalian RGCs do not regenerate, it is important to develop approaches that maintain the health of a patient’s remaining RGCs, so as to reduce or prevent additional vision loss.

This project aims to use RGCs derived from human stem cells to better understand how NF1 mutations lead to RGC damage and cell loss and to develop strategies to promote RGC survival and function. NF1 RGCs will be generated from small skin biopsy or blood samples from patients with NF1 mutations. These patient-derived cells will then be studied to uncover how their mutations affect the RGCs, and then we will test thousands of small molecules to try to identify ones that can reverse the effect of the NF1 mutation. It is hoped that these studies will lead to the development of potential drugs to preserve the vision of patients suffering from NF1.