Pranjal Kashyap
Research Mentor(s): Sebastian Werneburg
Mentor Department: Ophthalmology and Visual Sciences
Authors: Pranjal Kashyap, Jenna Staples, Sebastian Werneburg
Session: Session 6 (3:00pm – 3:50pm)
Presentation Type: Poster 89
Abstract
Multiple Sclerosis (MS) is a neurodegenerative disease historically characterized by chronic inflammation, demyelination, and neuroaxonal loss in the central nervous system. While disease-modifying therapies are available, no treatment halting progressive neurodegeneration has been developed. Degeneration of the visual system is a frequent early symptom of MS, often linked to retinal ganglion cells (RGCs) pathology. RGCs are neurons that originate in the retina and project into the brain where they form synapses onto relay neurons in the lateral geniculate nucleus (LGN), a processing center of visual information in the brain. Our lab has previously identified RGC synapse loss within the LGN that impaired visual function and occurred prior to demyelination or neuroaxonal loss. More recently, we also made the intriguing observation that RGCs can partially recover synapses during phases of repair. However, how synaptic restoration is regulated and why it is incomplete remains unknown. Previous work has established that neuronal activity is a crucial regulator of synaptic formation, but the impact of neuronal activity on synaptic repair in MS has not been studied yet. To test this, we use the MS-relevant preclinical cuprizone mouse model of de- and remyelination and manipulate RGC activity in the visual system by depriving mice from light stimulation in a 24h dark room compared to controls that were housed under normal light-dark conditions. Here we will present data showing whether reducing neuronal firing of RGCs during repair stages affects synaptic recovery in cuprizone mice. We will utilize postmortem brain section and immunohistochemistry and validate the reduction of RGC activity and quantify RGC synaptic densities in the LGN. This work will contribute to our understanding of functionally-relevant synaptic alterations in MS-relevant disease models, and in the process reveal potential new therapeutic targets.
