The cells we are interested in and focus on are called glia cells, more precisely Müller glia. Müller glia are the predominant glia in the neural retina and named after Professor Heinrich Müller (described in 1851). Glia cells per se are known as the support cells in the central nervous system, have a variety of other functions including maintaining the homeostasis of the tissue, but also protection after injury or disease. Glia cells, as part of their protective function, undergo morphological changes to create a barrier and a non-permissive environment for regeneration. This glial response, called gliosis, is a very complex process and includes a variety of factors and mechanisms which are not fully understood.
Molecules known to play in role in Müller glia development and function are microRNAs. microRNAs are small molecules present in every cell of the body that act as translational repressors. That means mRNA (transcribed from DNA) is not translated into protein. About 1000 different microRNAs have been identified so far and it is known that they have an impact in development, independent from tissue origin and cell type. However, their expression pattern can vary between different cell types, developmental stages (maturation of a cell), as well as physiological and pathophysiological conditions. For the latter, there is increasing evidence that microRNAs play an important role in various diseases and can be used as a biomarker for certain diseases.
The Role of microRNAs in Retinal Glia Function
In our laboratory, we investigate the impact of microRNAs in the different phases of glial activation after injury and/or disease. This will give us a better understanding of the underlying mechanisms of gliosis in order to develop strategies to minimize the inhibitory nature of this process. The long-term goal is to develop new approaches and therapies to attenuate the glial response after damage which might allow neuroprotection and partial regeneration in the neural retina as part of the central nervous system.
Established methods in the lab include, primary glia culture, organotypic explant cultures, microRNA profiling, RNA-sequencing, gene editing, protein assays, microscopy including time lapse, in vivo applications and much more.
1: The set of microRNAs present in Müller glia in vivo and in vitro
The specific set of microRNAs highly expressed in Müller glia (mGliomiRs) and neurons as well as a set of microRNAs similarly expressed in glia and neurons (shared miRs) were identified.
Wohl, S. G. and Reh, T.A., 2016. The microRNAs expression profile of mouse Müller glia in vivo and in vitro. Scientific Reports 6, 35423; doi 10.1038/srep35423.
2: microRNAs can convert Müller glia into neurons
The microRNAs miR-124, miR-9, and miR-9* can reprogram Müller glia into retinal progenitor cells that give rise to retinal neurons. The combination of miR-124/9/9* together with the transcription factor Ascl1 accelerates reprogramming.
Wohl, S. G. and Reh, T.A., 2016. miR-124-9-9* potentiates Ascl1-induced reprogramming of cultured Müller glia. Glia 64, 743-762.
3: microRNAs are required for Müller glia function (DicerCKO)
Deleting Dicer, the enzyme that generates mature microRNAs, in Müller glia cells leads to a disruption in the retinal architecture. Müller glia proliferate and migrate and do not function properly anymore. As a consequence, photoreceptors die and a phenotype that resembles retinitis pigmentosa can be observed over time (see main website image: Dicer cKO 6 months after Dicer deletion).
Wohl, S. G., Jorstad, N. L., Levine, E., and Reh, T.A., 2017: Müller glial microRNAs are required for the maintenance of glial homeostasis and retinal architecture. Nature Communications, 8(1):1603. DOI: 10.1038/s41467-017-01624
Are you interested in becoming part of our team? We are currently seeking highly motivated postdocs, graduate students and interns/trainees with interest in cellular and molecular vision science to join our lab!
For more info about the PhD student programs see https://www.sunyopt.edu/education/admissions/graduate_programs
For general inquiries, please use the contact form below. For an application, please sent your letter and detailed CV to firstname.lastname@example.org.
Stefanie G. Wohl, Principal Investigator
Stefanie received her Bachelors and Masters of Science from the Friedrich Schiller University of Jena, in Germany. Her graduate work focused on the identification of putative stem-cell like cells after moderate and severe injury which also included the study of neurodegeneration and immunological cell responses. She discovered a subtype of microglia that transiently increase in number after optic nerve injury expressing a marker that was primarily associated with stem/ progenitor cells. Stefanie received her PhD (neuroscience/ ophthalmology) with highest honors (summa cum laude) from the Friedrich Schiller University of Jena in 2011. For her post-doc training, she decided to go abroad and joined the laboratory of Tom Reh at the University of Washington in Seattle. During this time she discovered her interest in microRNAs and focused her research on Müller glia. In September 2018, Stefanie became Assistant Professor at the State University of New York, College of Optometry in the Department of Biological and Vision Sciences. Her new laboratory is the first of the new Center for Translational Vision Research at the college and will focus on the role of microRNAs in retinal glial function.
Stefanie was a recipient of a Research Fellowship from the German Research Foundation (DFG, 2014-2016) and the New York State Empire Innovator Grant (2018-2021).
Monica Andrade, Senior Research Support Specialist
Monica joined the lab in 2019 as a Senior Research Support Specialist. She received her Bachelor of Arts from Rutgers University in New Brunswick, NJ with Biology as a major. She received a Master of Science from Long Island University, Brooklyn campus, with Medical Microbiology as a specialty.
She worked in multiple projects involving epigenetic studies of the transcriptional repressor Zinc finger protein 57homolog (ZFP57), characterization and biological function of recombinant tissue factor pathway inhibitor beta (TFPIß), and the construction of 16S rRNA libraries for studies of the human microbiome.
The State University of New York
College of Optometry
Department of Biological and Vision Sciences
33W 42nd Street 10036, New York, NY
Phone office: +1 212 938 4069
Phone lab: +1 212 938 5822
Schultz, R., Krug, M., Precht, M., Wohl, S.G., Witte, O.W., Schmeer, C., 2018: Frataxin overexpression in Müller cells protects retinal ganglion cells in a mouse model of ischemia/reperfusion injury in vivo. Scientific Reports 8, doi:10.1038/s41598-018-22887-5.
Wohl, S. G., Jorstad, N. L., Levine, E., and Reh, T.A., 2017: Müller glial microRNAs are required for the maintenance of glial homeostasis and retinal architecture. Nature Communications, 8(1):1603. DOI: 10.1038/s41467-017-01624-y.
Jorstad, N. L., Wilken, M. S., Grimes, W. N., Wohl, S. G., VandenBosch L., Yoshimatsu T., Wong R. O., Rieke F., and Reh, T.A., 2017: Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature 548, 103-107, DOI: 10.1038/nature23283.
Wohl, S. G., Schmeer, C. W., Witte, O. W., and Isenmann, S., 2010. Proliferative response of microglia and macrophages in the adult mouse eye after optic nerve lesion. Investigative Ophthalmology & Visual Science 51, 2686-2696.
Wohl, S. G., Schmeer, C. W., Kretz, A., Witte, O. W., and Isenmann, S., 2009. Optic nerve lesion increases cell proliferation and Nestin expression in the adult mouse eye in vivo. Experimental Neurology 219, 175-186.