Optimizing Visual Recovery Using Nf1 Genetically Engineered Mice

Using a novel collection of different Nf1-mutant mouse strains engineered in the Gutmann laboratory to develop OPGs similar to those arising in children with NF1, this project will conduct a series of experiments and studies to (1) identify the critical therapeutic intervention intervals for durable visual recovery across multiple preclinical Nf1-OPG mouse strains, (2) define the mechanisms underlying increased Nf1-mutant retinal ganglion cell (RGC) intrinsic vulnerability across multiple preclinical Nf1-OPG mouse strains by focusing on Nf1- dependent cyclic AMP regulation in RGCs, (3) define the mechanisms underlying increased Nf1-mutant microglia-induced retinal ganglion cell death across multiple preclinical Nf1-OPG mouse strains, and (4) perform proof-of-concept preclinical
evaluations of current (MEK inhibitors) and novel neurorestorative therapies that result from collaborative efforts with investigators in the GFF VRI.