Functional and anatomical characterizations of retinal ganglion cell degeneration in a murine model of Neurofibromatosis type 1

National Eye Institute

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Abstract

First, we examined the overall visual function using optomotor reflex test, which revealed a significant decrease of visual sensitivity and acuity, but interestingly, with a large variation similar to human patients. However, optical tomography coherence revealed a consistent thinning in the central retina. To further explore the origin of the visual defect, we characterized pathological changes along the visual pathway. Although the gliomas are often localized in the pre-chiasm region, common signs of degeneration such as axonal disruption, astrogliosis, and microglial activation can be found in the optic nerve, and optic track towards higher visual regions in the brain. In the retina, we discovered several degenerative patterns of retinal ganglion cells (RGCs), verified by measuring the accumulation of neurofilaments in their somas and apoptosis markers. In addition, ex vivo recordings confirmed the abnormality of RGCs. These results provide the first systematic characterization of the pathophysiology along the visual pathway in an NF1 animal model. The multiple sites of degenerative phenotype provide a possible explanation of the variable visual symptoms that are often poorly correlated with the tumor size in clinical observations. In addition, this study provides a foundation for further understanding the timing of different pathological changes, and possibly define a window for a viable treatment for NF1 patients.