Research Interests
The Role of microRNAs in Retinal Glia Function
My laboratory studies the neural retina at the cellular and molecular level. 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 but have a variety of other functions including maintaining the homeostasis of the tissue but also protection after injury or disease.
In mammals, including humans, the central nervous system i.e., the brain (including the retina) and the spinal cord, does not regenerate after injury or disease. We know that glia, 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 a huge 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.
In my laboratory, we investigate the role of microRNAs in the glial response to injury/disease as well as for cell replacement therapies by reprogramming Müller glia into retinal neurons. The focus lies on Müller glia but will also include other glia types such as astrocytes and microglia. Specific approaches are
1) Transgenic models to visualize and isolate the different kind of glia
2) Cell and tissue culture to study cellular and molecular changes in glia
3) microRNA profiling and mRNA analyses
4) Techniques to overexpress or inhibit microRNAs and alter protein expression
5) identification of biomarkers for retinal diseases
6) Development and implementation of cell replacement therapies using glial cells
Investigating the impact of microRNAs in the different phases of glial activation after injury and/or disease 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 regeneration of the central nervous system including the neural retina.
Publications
- View in microRNAs as a potential tool to fight blindness: focus on Müller glia and gliosis, Neural Regeneration Research 17 (7): 1501-1502 1501-1502, 2022
- A comparative analysis of reactive Muller glia gene expression after light damage and microRNA-depleted Muller glia - Focus on microRNAs, Fontiers in Cell and Developmental Biology 8 (620459): 2021
- Retinal miRNA functions in health and disease, Molecular Therapies for Inherited Retinal Diseases 2020
- Developmental changes in the accessible chromatin, transcriptome and Ascl1-binding correlate with the loss in Muller glia regnerative potential, Scientific Reports 10 (13615): 2020
- Retinal miRNA Functions in Health and Disease, Genes 10 (5): 2019
- Cis-Regulatory Accessibility Directs Muller Glial Development and Regenerative Capacity, BioRxiv 2019
- microRNAs miR-25 and let-7 promote a neurogenic potential of Muller glia in mice., Development 146 2019
- Frataxin overexpression in Muller cells protects retinal ganglion cells in a mouse model of ischemia/reperfusion injury in vivo, Sci Rep 8 (1): 4846 4846, 2018
- Stimulation of functional neuronal regeneration from Muller glia in adult mice, Nature 548 (7665): 103-107 103-107, 2017
- Muller glial microRNAs are required for the maintenance of glial homeostasis and retinal architecture., Nature Communications 8 1603 1603, 2017
- miR-124-9-9* potentiates Ascl1-induced reprogramming of cultured Muller glia, Glia 64 (5): 743-62 743-62, 2016
- The microRNA expression profile of mouse Muller glia in vivo and in vitro. , The microRNA expression profile of mouse Muller glia in vivo and in vitro. 6 35423 35423, 2016
- Cell-replacement therapy and neural repair in the retina, Cell Tissue Res 349 (1): 363-74 363-74, 2012
- Neurogenic potential of stem/progenitor-like cells in the adult mammalian eye, Prog Retin Eye Res 31 (3): 13-42 13-42, 2012
- In situ dividing and phagocytosing retinal microglia express nestin, vimentin, and NG2 in vivo, PLoS One 6 (8): e22408 e22408, 2011
- Proliferative response of microglia and macrophages in the adult mouse eye after optic nerve lesion, Invest Ophthalmol Vis Sci 51 (5): 2686-96 2686-96, 2010
- Optic nerve lesion increases cell proliferation and nestin expression in the adult mouse eye in vivo, Exp Neurol 219 (1): 175-86 175-86, 2009
Presentations
- The role of microRNA in Muller glia function: glial reprogramming, 2021
Oral Presentation
- The role of microRNAs in Müller glia reprogramming, 2020
Oral Presentation
- The Role of microRNAs in Early Postnatal Retinal Development, 2020
Poster
- The role of miRNAs in Gliosis, 2020
Oral Presentation
- Muller glia lose neurogenic potential over development, 2019
Poster
- The impact of the loss of Muller glia microRNAs in Muller glia function, 2019
Oral Presentation
- The microRNA and mRNA profile of Müller glia after light damage, 2018
Poster
- Changes in Müller glia microRNAs after light damage, 2018
Poster
- microRNAs and Muller glia, 2017
Oral Presentation
- The role microRNAs in Muller glia function and retinal architecture, 2017
Oral Presentation
- microRNAs are required for maintenance of Müller glia homeostasis and retinal architecture, 2017
Oral Presentation
- microRNAs in Muller glia function and reprogramming, 2017
Oral Presentation
- A potential role for epigenetic repression in retinal regeneration, 2016
Poster
- Dicer conditional knock out in mature Müller glia leads to upregulation of Brevican and disorganization of the retinal structure, 2016
Poster
- Changes in microRNAs after injury and Dicer deletion, 2016
Poster
- The Role of miR-124-9-9* in Müller glia reprogramming, 2014
Poster
- Microglia cell proliferation in the ipsi- and contralateral retina after acute retinal ischemia/reperfusion in the mouse retina in vivo, 2013
Oral Presentation
- Retinal microglia response following optic nerve injury and retinal ischemia, 2012
Oral Presentation
- Adult retinal microglia express neural markers nestin and NG2 which are involved in cell proliferation and phagocytosis, 2011
Poster
- Erythropoietin (EPO) and EPO receptor expression patterns in neuronal and glial cells of the adult retina after optic nerve lesion, 2011
Poster
- Injury-induced proliferation of glial cells, 2011
Oral Presentation
- Microglia/macrophage proliferative response in the adult rat retina after optic nerve and retinal lesion - a comparative study of cell proliferation potential and nestin expression., 2010
Poster
- Microglia proliferate and express nestin following ON transection in the adult rat retina, 2009
Poster
- Optic nerve transection and crush lesion increases cell proliferation in the adult rat retina, 2008
Poster
- Lesion-induced generation of putative neural progenitor cells in the adult rat retina, 2007
Poster
- Microglia after optic nerve injury and ischemia, 2006
Oral Presentation
- Optic nerve lesion induces potential neural progenitor cell proliferation in the adult mouse retina, 2006
Poster
- Lesion-induced generation of neural cells in the adult rodent retina., 2005
Poster
