Müller glia

Müller glia, or Müller cells, are a type of retinal glial cells, first recognized and described by Heinrich Müller.[1] They are found in the vertebrate retina, which serve as support cells for the neurons, as all glial cells do. They are the most common type of glial cell found in the retina. While their cell bodies are located in the inner nuclear layer of the retina, they span across the entire retina.[2]

3D animation of Müller cell processes (red) interconnected with a retinal microglia cell (green).

The major role of the Müller cells is to maintain the structural and functional stability of retinal cells. This includes regulation of the extracellular environment via uptake of neurotransmitters, removal of debris, regulation of K+ levels, storage of glycogen, electrical insulation of receptors and other neurons, and mechanical support of the neural retina.


Müller glia are derived developmentally from two distinct populations of cells. They are the only retinal glial cell that shares a common cell lineage with retinal neurons. However, a subset of Müller glia has been shown to originate from neural crest cells.[3] They are to be critical to the development of the retina in mice, serving as promoters of retinal growth and histogenesis via a non-specific esterase mediated mechanism.[4] Müller glia have also been implicated to serve as guidepost cells for the developing axons of neurons in the chick retina.[5] Studies using a zebrafish model of Usher syndrome have implicated a role for Müller glia in synaptogenesis, the formation of synapses.[6]

Neuronal support

Spatial relationship between Müller cells and microglia

As glial cells, Müller glia serve a secondary but important role to neurons. As such, they have been shown to serve as important mediators of neurotransmitter (acetylcholine and GABA specifically) degradation and maintenance of a favorable retinal microenvironment in turtles.[7] Müller glia have also been shown to be important in the induction of the enzyme glutamine synthetase in chicken embryos,[8] which is an important actor in the regulation of glutamine and ammonia concentrations in the central nervous system. Müller glia have been further identified as fundamental to the transmission of light through the vertebrate retina due to their unique funnel shape, orientation within the retina and more favorable physical properties.[9]

Use in research

Müller glia are currently being studied for their role in neural regeneration, a phenomenon which is not known to occur in humans.[10] Studies to this end of Müller glia in both the zebrafish[11][12] and chicken[13] retina have been performed, with the exact molecular mechanism of regeneration remaining unclear. Further studies performed in mice have shown that overexpression of Ascl1 in Müller glia in conjunction with administration of a histone deacteylase inhibitor allowed for regeneration of retinal neurons from Müller glia.[14] Studies in human models have demonstrated that Müller glia have the potential to serve as stem cells in the adult retina[15] and are efficient rod photoreceptor progenitors.[16]

Damage to retinal cells results in Müller cells to undergo gliosis. The result of the response varies depending on the damage and the organism in which this damage occurred.[2][17] It has been shown in zebrafish that Müller glia undergo dedifferentiation into multipotent progenitor cells. The progenitor cell can then divide and differentiate into a number of retinal cell types, including photoreceptor cells, that may have been damaged during injury.[18] Additionally, further research has shown that Müller glia act as light collectors in the mammalian eye, analogous to the fiber optic plate, funneling light to the rod and cone photoreceptors.[9]

Aquaporin-4 in Müller cell in rat, transfer water to vitreous body.[19][20]

It was reported that Müller cells can be damaged by niacin overdose.[21][22]

See also


  1. Müller, Heinrich (1851). "Zur Histologie der Netzhaut" (PDF). Zeitschrift für Wissenschaftliche Zoologie. 3: 234–237.
  2. Goldman, Daniel (July 2014). "Müller glia cell reprogramming and retina regeneration". Nature Reviews Neuroscience. 15 (7): 431–442. doi:10.1038/nrn3723. PMC 4249724. PMID 24894585.
  3. Hamon, Annaïg; et al. (October 2015). "Müller Glial Cell-Dependent Regeneration of the Neural Retina: An Overview Across Vertebrate Model Systems". Developmental Dynamics. 245 (7): 727–738. doi:10.1002/DVDY.24375. PMC 4900950. PMID 26661417.
  4. Bhattacharjee, J; Sanyal, S (1975). "Developmental origin and early differentiation of retinal Müller cells in mice". Journal of Anatomy. 120 (Pt 2): 367–72. PMC 1231976. PMID 1201967.
  5. Meller, K.; Tetzlaff, W. (1976). "Scanning electron microscopic studies on the development of the chick retina". Cell and Tissue Research. 170 (2). doi:10.1007/bf00224296.
  6. Phillips, J. B.; Blanco-Sanchez, B.; Lentz, J. J.; Tallafuss, A.; Khanobdee, K.; Sampath, S.; Jacobs, Z. G.; Han, P. F.; Mishra, M.; Titus, T. A.; Williams, D. S.; Keats, B. J.; Washbourne, P.; Westerfield, M. (2011). "Harmonin (Ush1c) is required in zebrafish Muller glial cells for photoreceptor synaptic development and function". Disease Models & Mechanisms. 4 (6): 786–800. doi:10.1242/dmm.006429. PMC 3209648. PMID 21757509.
  7. Sarthy, P.; Lam, D. M. (1978). "Biochemical studies of isolated glial (muller) cells from the turtle retina". The Journal of Cell Biology. 78 (3): 675–84. doi:10.1083/jcb.78.3.675. PMC 2110200. PMID 29902.
  8. Linser, P.; Moscona, A. A. (1979). "Induction of glutamine synthetase in embryonic neural retina: Localization in Muller fibers and dependence on cell interactions". Proceedings of the National Academy of Sciences. 76 (12): 6476–80. Bibcode:1979PNAS...76.6476L. doi:10.1073/pnas.76.12.6476. PMC 411888. PMID 42916.
  9. Franze, K.; Grosche, J.; Skatchkov, S. N.; Schinkinger, S.; Foja, C.; Schild, D.; Uckermann, O.; Travis, K.; Reichenbach, A.; Guck, J. (2007). "Muller cells are living optical fibers in the vertebrate retina". Proceedings of the National Academy of Sciences. 104 (20): 8287–92. Bibcode:2007PNAS..104.8287F. doi:10.1073/pnas.0611180104. PMC 1895942. PMID 17485670. Lay summary The Register (1 May 2007).
  10. WebVision: Regeneration in the Visual System of Adult Mammals
  11. Fausett, B. V.; Goldman, D. (2006). "A Role for α1 Tubulin-Expressing Müller Glia in Regeneration of the Injured Zebrafish Retina". Journal of Neuroscience. 26 (23): 6303–13. doi:10.1523/jneurosci.0332-06.2006. PMID 16763038.
  12. Raymond, Pamela A; Barthel, Linda K; Bernardos, Rebecca L; Perkowski, John J (2006). "Molecular characterization of retinal stem cells and their niches in adult zebrafish". BMC Developmental Biology. 6: 36. doi:10.1186/1471-213X-6-36. PMC 1564002. PMID 16872490.
  13. Fischer, Andy J.; Reh, Thomas A. (2001). "Müller glia are a potential source of neural regeneration in the postnatal chicken retina". Nature Neuroscience. 4 (3): 247–52. doi:10.1038/85090. PMID 11224540.
  14. Jorstad, Nikolas L.; Wilken, Matthew S.; Grimes, William N.; Wohl, Stefanie G.; VandenBosch, Leah S.; Yoshimatsu, Takeshi; Wong, Rachel O.; Rieke, Fred; Reh, Thomas A. (August 2017). "Stimulation of functional neuronal regeneration from Müller glia in adult mice". Nature. 548 (7665): 103–107. Bibcode:2017Natur.548..103J. doi:10.1038/nature23283. PMC 5991837. PMID 28746305.
  15. Bhatia, Bhairavi; Jayaram, Hari; Singhal, Shweta; Jones, Megan F.; Limb, G. Astrid (2011). "Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye". Experimental Eye Research. 93 (6): 852–61. doi:10.1016/j.exer.2011.09.015. PMC 3268355. PMID 21989110.
  16. Giannelli, Serena G.; Demontis, Gian Carlo; Pertile, Grazia; Rama, Paolo; Broccoli, Vania (2011). "Adult Human Müller Glia Cells Are a Highly Efficient Source of Rod Photoreceptors". Stem Cells. 29 (2): 344–56. doi:10.1002/stem.579. PMID 21732491.
  17. Bringmann, Andreas; Iandiev, Ianors; Pannicke, Thomas; Wurm, Antje; Hollborn, Margrit; Wiedemann, Peter; Osborne, Neville N.; Reichenbach, Andreas (November 2009). "Cellular signaling and factors involved in Müller cell gliosis: Neuroprotective and detrimental effects". Progress in Retinal and Eye Research. 28 (6): 423–451. doi:10.1016/j.preteyeres.2009.07.001. PMID 19660572.
  18. Bernardos, R. L.; Barthel, L. K.; Meyers, J. R.; Raymond, P. A. (2007). "Late-Stage Neuronal Progenitors in the Retina Are Radial Muller Glia That Function as Retinal Stem Cells". Journal of Neuroscience. 27 (26): 7028–40. doi:10.1523/JNEUROSCI.1624-07.2007. PMID 17596452.
  19. Simó, Rafael; Villarroel, Marta; Corraliza, Lídia; Hernández, Cristina; Garcia-Ramírez, Marta (2010). "The Retinal Pigment Epithelium: Something More than a Constituent of the Blood-Retinal Barrier—Implications for the Pathogenesis of Diabetic Retinopathy". Journal of Biomedicine and Biotechnology. 2010: 1–15. doi:10.1155/2010/190724. PMC 2825554. PMID 20182540.
  20. Jo, A. O.; Ryskamp, D. A.; Phuong, T. T. T.; Verkman, A. S.; Yarishkin, O.; MacAulay, N.; Kri Aj, D. (2015). "TRPV4 and AQP4 Channels Synergistically Regulate Cell Volume and Calcium Homeostasis in Retinal Muller Glia". Journal of Neuroscience. 35 (39): 13525–37. doi:10.1523/JNEUROSCI.1987-15.2015. PMC 4588615. PMID 26424896.
  21. "Eye damage linked to popular over-the-counter vitamin that lowers cholesterol can be reversed". Science X network: Medical Xpress. 29 October 2019.
  22. Lee, Jessica G.; Patel, Anu; Bertolucci, Alessandra; Rosen, Richard B. (2019). "Optical Coherence Tomography, Fluorescein Angiography, and Electroretinography Features of Niacin Maculopathy: New Insight Into Pathogenesis". Journal of VitreoRetinal Diseases: 247412641987756. doi:10.1177/2474126419877567. ISSN 2474-1264.
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