Abstract
Müller glia (MG) are the predominant glia in the neural retina and become reactive after injury or in disease. microRNAs (miRNAs) are translational repressors that regulate a variety of processes during development and are required for MG function. However, no data is available about the MG miRNAs in reactive gliosis. Therefore, in this study, we aimed to profile miRNAs and mRNAs in reactive MG 7 days after light damage. Light damage was performed for 8 h at 10,000 lux; this leads to rapid neuronal loss and strong MG reactivity. miRNAs were profiled using the Nanostring platform, gene expression analysis was conducted via microarray. We compared the light damage dataset with the dataset of Dicer deleted MG in order to find similarities and differences. We found: (1) The vast majority of MG miRNAs declined in reactive MG 7 days after light damage. (2) Only four miRNAs increased after light damage, which included miR-124. (3) The top 10 genes found upregulated in reactive MG after light damage include Gfap, Serpina3n, Ednrb and Cxcl10. (4) The miRNA decrease in reactive MG 7 days after injury resembles the profile of Dicer-depleted MG after one month. (5) The comparison of both mRNA expression datasets (light damage and Dicer-cKO) showed 1,502 genes were expressed under both conditions, with Maff , Egr2, Gadd45b, and Atf3 as top upregulated candidates. (6) The DIANA-TarBase v.8 miRNA:RNA interaction tool showed that three miRNAs were found to be present in all networks, i.e., after light damage, and in the combined data set; these were miR-125b-5p, let-7b and let-7c. Taken together, results show there is an overlap of gene regulatory events that occur in reactive MG after light damage (direct damage of neurons) and miRNA-depleted MG (Dicer-cKO), two very different paradigms. This suggests that MG miRNAs play an important role in a ubiquitous MG stress response and manipulating these miRNAs could be a first step to attenuate gliosis.
Highlights
Müller glia (MG) are the predominant glia in the neural retina and fulfill, similar to astrocytes in the brain, a variety of crucial functions to ensure retinal homeostasis and proper neuronal function
We found that the vast majority of miRNAs highly expressed in MG declined after light damage, similar to what we found in the Dicer-cKOMG
We previously profiled the miRNAs highly expressed in MG (Wohl and Reh, 2016) and found that they are required for proper MG function, which in turn is required for proper retinal architecture and retinal health (Wohl et al, 2017)
Summary
Müller glia (MG) are the predominant glia in the neural retina and fulfill, similar to astrocytes in the brain, a variety of crucial functions to ensure retinal homeostasis and proper neuronal function These functions include neurotransmitter uptake and recycling via specific enzymes such as glutamine synthetase (GS), nourishment of neurons by providing lactate, tissue stabilization and structural support by forming the inner and outer limiting membrane, maintenance of the blood retinal barrier (BRB), and tissue protection (Reichenbach et al, 1993; Newman and Reichenbach, 1996; Bringmann et al, 2000, 2006; Bringmann and Reichenbach, 2001; Kuhrt et al, 2008; Reichenbach and Bringmann, 2013). The gliotic response requires substantial changes in gene expression and it is currently not known whether miRNAs play a role in this process
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
