Abstract
Müller glia are the principal macroglia of the retina and support retinal neurons both in health and disease. In retinitis pigmentosa (RP), a highly heterogeneous inherited retinal disorder, the most common form of pathology involves primary rod degeneration, followed by secondary cone death. To investigate Müller glia responses to rod degeneration, we performed droplet-based single-cell RNA sequencing in the rd10 mouse model of RP during primary rod degeneration. We confirmed known MG behavior on gliosis, metabolic, and immune functions. Pde6brd10 Müller glia also exhibited an increased expression of histocompatibility complex members, which might arise from a novel immune function of Müller glia in RP. We also describe a possible decrease in glial lipid biogenesis, which might affect degenerating photoreceptors.
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References
Berson EL, Rosner B, Sandberg MA, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004;122:1306–14.
Bringmann A, Pannicke T, Grosche J, et al. Müller cells in the healthy and diseased retina. Prog Retin Eye Res. 2006;25:397–424.
Butler A, Hoffman P, Smibert P, et al. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36:411–20.
Gao Z, Lee P, Stafford JM, et al. An AUTS2-Polycomb complex activates gene expression in the CNS. Nature. 2014;516:349–54.
Gargini C, Terzibasi E, Mazzoni F, Strettoi E. Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J Comp Neurol. 2007;500:222–38.
Hamano F, Kuribayashi H, Iwagawa T, et al. Mapping membrane lipids in the developing and adult mouse retina under physiological and pathological conditions using mass spectrometry. J Biol Chem. 2021;296:100303.
Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795–809.
Heng JS, Hackett SF, Stein-O’Brien GL, et al. Comprehensive analysis of a mouse model of spontaneous uveoretinitis using single-cell RNA sequencing. Proc Natl Acad Sci U S A. 2019;116:26734–44.
Hoang T, Wang J, Boyd P, et al. Gene regulatory networks controlling vertebrate retinal regeneration. Science. 2020; https://doi.org/10.1126/science.abb8598.
Huang J, Possin DE, Saari JC. Localizations of visual cycle components in retinal pigment epithelium. Mol Vis. 2009;15:223–34.
Ilicic T, Kim JK, Kolodziejczyk AA, et al. Classification of low quality cells from single-cell RNA-seq data. Genome Biol. 2016;17:29.
Joly S, Lange C, Thiersch M, et al. Leukemia inhibitory factor extends the lifespan of injured photoreceptors in vivo. J Neurosci. 2008;28:13765–74.
Joly S, Pernet V, Samardzija M, Grimm C. Pax6-positive Müller glia cells express cell cycle markers but do not proliferate after photoreceptor injury in the mouse retina. Glia. 2011;59:1033–46.
Lorenz L, Hirmer S, Schmalen A, et al. Cell surface profiling of retinal Müller glial cells reveals association to immune pathways after LPS stimulation. Cell. 2021;10 https://doi.org/10.3390/cells10030711.
Newton F, Megaw R. Mechanisms of photoreceptor death in retinitis pigmentosa. Genes. 2020;11 https://doi.org/10.3390/genes11101120.
Noailles A, Maneu V, Campello L, et al. Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration. Sci Rep. 2016;6:33356.
Otake H, Yamamoto T, Deguchi S, et al. Retinal proteomic evaluation of rats following streptozotocin-injection using shotgun proteomics. Mol Med Rep. 2020;21:379–86.
Phillips MJ, Otteson DC, Sherry DM. Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa. J Comp Neurol. 2010;518:2071–89.
Politi L, Rotstein N, Carri N. Effects of docosahexaenoic acid on retinal development: cellular and molecular aspects. Lipids. 2001;36:927–35.
Roesch K, Jadhav AP, Trimarchi JM, et al. The transcriptome of retinal Müller glial cells. J Comp Neurol. 2008;509:225–38.
Roesch K, Stadler MB, Cepko CL. Gene expression changes within Müller glial cells in retinitis pigmentosa. Mol Vis. 2012;18:1197–214.
Todd L, Palazzo I, Suarez L, et al. Reactive microglia and IL1β/IL-1R1-signaling mediate neuroprotection in excitotoxin-damaged mouse retina. J Neuroinflammation. 2019;16:118.
Ueki Y, Le Y-Z, Chollangi S, et al. Preconditioning-induced protection of photoreceptors requires activation of the signal-transducing receptor gp130 in photoreceptors. Proc Natl Acad Sci U S A. 2009;106:21389–94.
Vance JE, Tasseva G. Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells. Biochim Biophys Acta. 2013;1831:543–54.
Wang J-S, Kefalov VJ. The cone-specific visual cycle. Prog Retin Eye Res. 2011;30:115–28.
Acknowledgments
The authors would like to thank the Functional Genomics Center Zürich for their excellent guidance and assistance with scRNAseq. This study was supported by the Swiss National Science Foundation (grant nr. 31003A_173008).
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Sigurdsson, D., Grimm, C. (2023). Single-Cell Transcriptomic Profiling of Müller Glia in the rd10 Retina. In: Ash, J.D., Pierce, E., Anderson, R.E., Bowes Rickman, C., Hollyfield, J.G., Grimm, C. (eds) Retinal Degenerative Diseases XIX. Advances in Experimental Medicine and Biology, vol 1415. Springer, Cham. https://doi.org/10.1007/978-3-031-27681-1_55
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DOI: https://doi.org/10.1007/978-3-031-27681-1_55
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