Poster abstracts

Poster number 75 submitted by Liv Taylor

Inhibitors of Differentiation (Ids) Regulate the Timing of Cell-Cycle Exit in Muller Glia-Derived Progenitors

Liv Taylor (Neuroscience Graduate Program), Evan Hawthorn, Snehal Patel, Andy Fischer (Department of Neuroscience)

Abstract:
Retinal diseases such as glaucoma, diabetic retinopathy, and macular degeneration cause severe vision impairment, which is estimated to double in the U.S. between 2015 and 2050.1 Muller glia (MG) are promising targets for retinal regeneration, due to their ability to reprogram into progenitor-like cells (MGPCs) and differentiate into retinal neurons in lower vertebrates.2 Chicks have a limited capacity for regeneration: retinal damage induces MGPCs, but very few MGPCs go on to regenerate neurons.3 Identifying key factors that regulate MGPC-to-neuron induction in chicks may contribute to future clinical treatments reversing vision loss in human patients with retinal diseases.
Inhibitors of Differentiation (Id) transcription factors show unique patterns of expression in chick Muller glia and MGPCs. Based on their prominent role in regulating cyclin-dependent kinases and other cell-cycle regulators, we hypothesized that they may suppress MGPCs from exiting the cell cycle and differentiating into neurons. We found that intraocularly delivering a pan-Id antagonist to retinas prior to retinal damage stunted MGPC proliferation in retinas observed at 3 days-post-injury (DPI). Further, we observed higher levels of cell cycle inhibitors and lower levels of m-phase markers in Muller glia of retinas treated with the inhibitor. Application of the Id inhibitor after MGPC induction (3-5 DPI) significantly increased the abundance of MG-derived amacrine-like cells observed at 11 DPI.
Collectively, our findings indicate that Id activity is necessary for MG to de-differentiate and proliferate, but that Ids also suppress the differentiation of MGPCs into neurons. Targeting Ids is a promising strategy for enhancing the neurogenic potential of MGPCs.

References:
1.Varma, R., Vajaranant, T. S., Burkemper, B., Wu, S., Torres, M., Hsu, C., Choudhury, F., & McKean-Cowdin, R. (2016). Visual Impairment and Blindness in Adults in the United States: Demographic and Geographic Variations From 2015 to 2050. JAMA ophthalmology, 134(7), 802–809. https://doi.org/10.1001/jamaophthalmol.2016.1284
2.Hitchcock, P. F., & Raymond, P. A. (1992). Retinal regeneration. Trends in neurosciences, 15(3), 103–108. https://doi.org/10.1016/0166-2236(92)90020-9
3.Fischer, A. J., & Reh, T. A. (2001). Müller glia are a potential source of neural regeneration in the postnatal chicken retina. Nature neuroscience, 4(3), 247–252. https://doi.org/10.1038/85090

Keywords: retinal regeneration, Muller Glia, reprogramming