Sean McCracken

Program: Neurosciences

Current advisor: Philip R. Williams, PhD

Undergraduate university: Johns Hopkins University, 2019

Enrollment year: 2020

Research summary
We study neurodegeneration using the retina as a model system. We want to improve our understanding of retinal ganglion cell differential survival after injury.

We have developed a method for in-vivo two-photon imaging of the mouse retina to observe individual neurons. This allows us to track cells over the time course of different manipulations, including injections of chemicals or injuries to retinal neurons. More specifically, I am using a physiological cytoplasmic Calcium (Ca2+) sensor, which when we express specifically in retinal ganglion cells (RGCs), gives us a baseline Ca2+ level of individual RGCs. We have identified a differential Ca2+ level across the RGC population within a single retina, and we hypothesized that this heterogeneity in Ca2+ could correlate with survival after injury. We then performed an Optic Nerve Crush (ONC) injury, which causes degeneration and death of most RGCs (~80% death over two weeks). We were able to track cells and correlate them with their baseline Ca2+ levels, and indeed we found that cells with higher baseline Ca2+ survive better than low Ca2+ cells. We plan to assess the mechanisms of Ca2+ differential by looking at different Ca2+ stores and also to manipulate Ca2+ levels to promote or reduce survival after injury.

Graduate publications
McCracken S, Fitzpatrick MJ, Hall AL, Wang Z, Kerschensteiner D, Morgan JL, Williams PR. 2023 Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo. Cell Rep, 42(10):113165. PMCID: PMC10947246

Johnson KP, Fitzpatrick MJ, Zhao L, Wang B, McCracken S, Williams PR, Kerschensteiner D. 2021 Cell-type-specific binocular vision guides predation in mice. Neuron, 109(9):1527-1539.e4. PMCID: PMC8112612

Wang Z, McCracken S, Williams PR. 2021 Transpupillary Two-photon In vivo Imaging of the Mouse Retina. J Vis Exp, (168):. PMCID: PMC9385267