Hostname: page-component-669899f699-7tmb6 Total loading time: 0 Render date: 2025-05-02T13:28:18.674Z Has data issue: false hasContentIssue false
  • English
  • Français

Glial cell response to constant low light exposure in rat retina

Published online by Cambridge University Press:  27 September 2022

Manuel G. Bruera ,
María M. Benedetto ,
Mario E. Guido ,
Alicia L. Degano  and
María A. Contin Open the ORCID record for María A. Contin [Opens in a new window]
Manuel G. Bruera
Affiliation:
Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina
María M. Benedetto
Affiliation:
Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina
Mario E. Guido
Affiliation:
Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina
Alicia L. Degano
Affiliation:
Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina
María A. Contin*
Affiliation:
Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina
*
Corresponding author: María A. Contin, email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

To study the macroglia and microglia and the immune role in long-time light exposure in rat eyes, we performed glial cell characterization along the time-course of retinal degeneration induced by chronic exposure to low-intensity light. Animals were exposed to light for periods of 2, 4, 6, or 8 days, and the retinal glial response was evaluated by immunohistochemistry, western blot and real-time reverse transcription polymerase chain reaction. Retinal cells presented an increased expression of the macroglia marker GFAP, as well as increased mRNA levels of microglia markers Iba1 and CD68 after 6 days. Also, at this time-point, we found a higher number of Iba1-positive cells in the outer nuclear layer area; moreover, these cells showed the characteristic activated-microglia morphology. The expression levels of immune mediators TNF, IL-6, and chemokines CX3CR1 and CCL2 were also significantly increased after 6 days. All the events of glial activation occurred after 5–6 days of constant light exposure, when the number of photoreceptor cells has already decreased significantly. Herein, we demonstrated that glial and immune activation are secondary to neurodegeneration; in this scenario, our results suggest that photoreceptor death is an early event that occurs independently of glial-derived immune responses.

Keywords

retinal degenerationlight damageretinal glial cellslight pollution
Type
Research Article
Information
Visual Neuroscience , Volume 39 , 2022 , E005
Check for updates
Copyright
© The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Ashwell, K.W.S., Holländer, H., Streit, W. & Stone, J. (1989). The appearance and distribution of microglia in the developing retina of the rat. Visual Neuroscience 2, 437–448.CrossRefGoogle ScholarPubMed
Baggiolini, M. & Dahinden, C.A. (1994). CC chemokines in allergic inflammation. Immunology Today 15, 127–133.CrossRefGoogle ScholarPubMed
Bazan, J.F., Bacon, K.B., Hardiman, G., Wang, W., Soo, K., Rossi, D., Greaves, D.R., Zlotnik, A. & Schall, T.J. (1997). A new class of membrane-bound chemokine with a CX3C motif. Nature 385, 640–642.CrossRefGoogle ScholarPubMed
Bejarano-Escobar, R., Blasco, M., Martín-Partido, G. & Francisco-Morcillo, J. (2012). Light-induced degeneration and microglial response in the retina of an epibenthonic pigmented teleost: Age-dependent photoreceptor susceptibility to cell death. Journal of Experimental Biology 215, 3799–3812.Google ScholarPubMed
Benedetto, M.M. & Contin, M.A. (2019). Oxidative stress in retinal degeneration promoted by constant LED light. Frontiers in Cellular Neuroscience 13, 1–11.CrossRefGoogle ScholarPubMed
Bringmann, A. & Wiedemann, P. (2011). Müller glial cells in retinal disease. Ophthalmologica 227, 1–19.CrossRefGoogle ScholarPubMed
Chahory, S., Keller, N., Martin, E., Omri, B., Crisanti, P. & Torriglia, A. (2010). Light induced retinal degeneration activates a caspase-independent pathway involving cathepsin D. Neurochemistry International 57, 278–287.CrossRefGoogle ScholarPubMed
Chao, C.C., Hu, S.X., Ehrlich, L. & Peterson, P.K. (1995). Interleukin-1 and tumor necrosis factor-α synergistically mediate neurotoxicity: Involvement of nitric oxide and of n-methyl-d-aspartate receptors. Brain Behavior and Immunity 9, 355–365.CrossRefGoogle ScholarPubMed
Checchin, D., Sennlaub, F., Levavasseur, E., Leduc, M. & Chemtob, S. (2006). Potential role of microglia in retinal blood vessel formation. Investigative Ophthalmology and Visual Science 47, 3595–3602.CrossRefGoogle ScholarPubMed
Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X. & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9, 7204–7218.CrossRefGoogle ScholarPubMed
Chen, L., Qi, Y. & Yang, X. (2015). Neuroprotective effects of Crocin against oxidative stress induced by ischemia/reperfusion injury in rat retina. Ophthalmic Research 54, 157–168.CrossRefGoogle ScholarPubMed
Chen, L., Wu, W., Dentchev, T., Zeng, Y., Wang, J., Tsui, I., Tobias, J.W., Bennett, J., Baldwin, D. & Dunaief, J.L. (2004). Light damage induced changes in mouse retinal gene expression. Experimental Eye Research 79, 239–247; doi:10.1016/j.exer.2004.05.002.CrossRefGoogle ScholarPubMed
Contín, M.A., Arietti, M.M., Benedetto, M.M., Bussi, C. & Guido, M.E. (2013). Photoreceptor damage induced by low-intensity light: Model of retinal degeneration in mammals. Molecular Vision 19, 1614–1625.Google ScholarPubMed
Contín, M.A., Benedetto, M.M., Quinteros-Quintana, M.L. & Guido, M.E. (2016). Light pollution: The possible consequences of excessive illumination on retina. Eye (London, England) 30, 255–263.CrossRefGoogle ScholarPubMed
Croisier, E., Moran, L.B., Dexter, D.T., Pearce, R.K.B. & Graeber, M.B. (2005). Microglial inflammation in the parkinsonian substantia nigra: Relationship to alpha-synuclein deposition. Journal of Neuroinflammation 2, 14; doi:10.1186/1742-2094-2-14.CrossRefGoogle ScholarPubMed
de Hoz, R., Rojas, B., Ramírez, A.I., Salazar, J.J., Gallego, B.I., Triviño, A. & Ramírez, J.M. (2016). Retinal macroglial responses in health and disease. BioMed Research International 2016, 1–13.CrossRefGoogle ScholarPubMed
Donovan, M., Carmody, R.J. & Cotter, T.G. (2001). Light-induced photoreceptor apoptosis in vivo requires neuronal nitric-oxide synthase and guanylate cyclase activity and is caspase-3-independent. The Journal of Biological Chemistry 276, 23000–23008.CrossRefGoogle ScholarPubMed
Donovan, M. & Cotter, T.G. (2002). Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and caspase-3 during retinal development. Cell Death and Differentiation 9, 1220–1231.CrossRefGoogle ScholarPubMed
Feng, L., Puyang, Z., Chen, H., Liang, P., Troy, J.B. & Liu, X. (2017b). Overexpression of brain-derived neurotrophic factor protects large retinal ganglion cells after optic nerve crush in mice. eNeuro 4, 0331–16.CrossRefGoogle Scholar
Feng, C.Y., Wang, X., Liu, T.J., Zhang, M., Xu, G.Z. & Ni, Y.Q. (2017a). Expression of CCL2 and its receptor in activation and migration of microglia and monocytes induced by photoreceptor apoptosis. Molecular Vision 23, 765–777.Google Scholar
Guido, M.E., Marchese, N.A., Rios, M.N., Morera, L.P., Diaz, N.M., Garbarino-Pico, E. & Contin, M.A. (2020). Non-visual opsins and novel photo-detectors in the vertebrate inner retina mediate light responses within the blue spectrum region. Cellular and Molecular Neurobiology 42, 59–83; doi:10.1007/s10571-020-00997-x.CrossRefGoogle ScholarPubMed
Hao, W., Wenzel, A., Obin, M.S., Chen, C.K., Brill, E., Krasnoperova, N.V., Eversole-Cire, P., Kleyner, Y., Taylor, A., Simon, M.I., Grimm, C., Reme, C.E. & Lem, J. (2002). Evidence for two apoptotic pathways in light-induced retinal degeneration. Nature Genetics 32, 254–260.CrossRefGoogle ScholarPubMed
Harada, T., Harada, C., Kohsaka, S., Wada, E., Yoshida, K., Ohno, S., Mamada, H., Tanaka, K., Parada, L.F. & Wada, K. (2002). Microglia–Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. The Journal of Neuroscience 22, 9228–9236; doi:10.1523/jneurosci.22-21-09228.2002.CrossRefGoogle ScholarPubMed
Kang, S., Larbi, D., Andrade, M., Reardon, S., Reh, T.A. & Wohl, S.G. (2021). A comparative analysis of reactive Müller glia gene expression after light damage and microRNA-depleted Müller glia—Focus on microRNAs. Frontiers in Cell and Developmental Biology 8, 620459; doi:10.3389/fcell.2020.620459.CrossRefGoogle ScholarPubMed
Karlen, S.J., Miller, E.B., Wang, X, Levine, E.S., Zawadzki, R.J. & Burns, M.E. (2018). Monocyte infiltration rather than microglia proliferation dominates the early immune response to rapid photoreceptor degeneration. Journal of Neuroinflammation 15, 344.CrossRefGoogle ScholarPubMed
Karlstetter, M., Ebert, S. & Langmann, T. (2010). Microglia in the healthy and degenerating retina: Insights from novel mouse models. Immunobiology 215, 685–691.CrossRefGoogle ScholarPubMed
Karlstetter, M., Scholz, R., Rutar, M., Wong, W.T., Provis, J.M. & Langmann, T. (2015). Retinal microglia: Just bystander or target for therapy? Progress in Retinal and Eye Research 45, 30–57.CrossRefGoogle ScholarPubMed
Karperien, A., Ahammer, H. & Jelinek, H.F. (2013). Quantitating the subtleties of microglial morphology with fractal analysis. Frontiers in Cellular Neuroscience 7, 1–34. doi:10.3389/fncel.2013.00003.CrossRefGoogle ScholarPubMed
Kreutzberg, G.W. (1996). Microglia: A sensor for pathological events in the CNS. Trends in Neurosciences 19, 312–318; doi:10.1016/0166-2236(96)10049-7.CrossRefGoogle ScholarPubMed
Kur, J., Newman, E.A. & Chan-Ling, T. (2012). Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Progress in Retinal and Eye Research 31, 377–406; doi:10.1016/j.preteyeres.2012.04.004.CrossRefGoogle ScholarPubMed
Langmann, T. (2007). Microglia activation in retinal degeneration. Journal of Leukocyte Biology 81, 1345–1351.CrossRefGoogle ScholarPubMed
Li, L., Eter, N. & Heiduschka, P. (2015). The microglia in healthy and diseased retina. Experimental Eye Research 136, 116–130; doi:10.1016/j.exer.2015.04.020.CrossRefGoogle ScholarPubMed
Liddelow, S.A., Guttenplan, K.A., Clarke, L.E., Bennett, F.C., Bohlen, C.J., Schirmer, L., Bennett, M.L., Münch, A.E., Chung, W.-S., Peterson, T.C., Wilton, D.K., Frouin, A., Napier, B.A., Panicker, N., Kumar, M., Buckwalter, M.S., Rowitch, D.H., Dawson, V.L., Dawson, T.M., Stevens, B. & Barres, B.A. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487; doi:10.1038/nature21029.CrossRefGoogle ScholarPubMed
Liu, C., Peng, M., Laties, A.M. & Wen, R. (1998). Preconditioning with bright light evokes a protective response against light damage in the rat retina. The Journal of Neuroscience 18, 1337–1344.CrossRefGoogle ScholarPubMed
Luo, W., Hu, H., Chang, R., Zhong, J., Knabel, M., O’Meally, R., Cole, R.N., Pandey, A. & Semenza, G.L. (2011). Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 145, 732–744; doi:10.1016/j.cell.2011.03.054.CrossRefGoogle ScholarPubMed
Masuda, T., Shimazawa, M. & Hara, H. (2017). Retinal diseases associated with oxidative stress and the effects of a free radical scavenger (Edaravone). Oxidative Medicine and Cellular Longevity 2017, 9208489; doi:10.1155/2017/9208489.CrossRefGoogle Scholar
Nelson, C.M., Ackerman, K.M., O’Hayer, P., Bailey, T.J., Gorsuch, R.A. & Hyde, D.R. (2013). Tumor necrosis factor-alpha is produced by dying retinal neurons and is required for Müller glia proliferation during Zebrafish retinal regeneration. Journal of Neuroscience 33, 6524–6539; doi:10.1523/JNEUROSCI.3838-12.2013.CrossRefGoogle ScholarPubMed
Organisciak, D., Wong, P., Rapp, C., Darrow, R., Ziesel, A., Rangarajan, R. & Lang, J. (2012). Light-induced retinal degeneration is prevented by zinc, a component in the age-related eye disease study formulation. Photochemistry and Photobiology 88, 1396–1407.CrossRefGoogle ScholarPubMed
Provis, J.M., Diaz, C.M. & Penfold, P.L. (1996). Microglia in human retina: A heterogeneous population with distinct ontogenies. Perspectives on Developmental Neurobiology 3, 213–222.Google ScholarPubMed
Quinteros Quintana, M.L., Benedetto, M.L., Maldonado, M.M., de Payer, E.A.C.V. & Contin, M.A. (2016). Electroretinography: A biopotential to assess the function/dysfunction of the retina. Journal of Physics: Conference Series 705, 012053.Google Scholar
Rajala, R.V.S., Rajala, A., Kooker, C., Wang, Y. & Anderson, R.E. (2016). The Warburg effect mediator pyruvate kinase M2 expression and regulation in the retina. Scientific Reports 6, 37727; doi:10.1038/srep37727.CrossRefGoogle ScholarPubMed
Rashid, K., Akhtar-Schaefer, I. & Langmann, T. (2019). Microglia in retinal degeneration. Frontiers in Immunology 10, 1–19.CrossRefGoogle ScholarPubMed
Reichenbach, A. & Bringmann, A. (2010). Müller cells in the healthy and Desease Retina. Springer, New York, NY. https//Doi.or/10.1007/978-1-4419-1672-3_2.CrossRefGoogle Scholar
Riccitelli, S., Di Paolo, M., Ashley, J., Bisti, S. & Di Marco, S. (2021). The timecourses of functional, morphological, and molecular changes triggered by light exposure in Sprague–Dawley Rat Retinas. Cells 10, 1561; doi:10.3390/cells10061561.CrossRefGoogle ScholarPubMed
Scholz, R., Sobotka, M., Caramoy, A., Stempfl, T., Moehle, C. & Langmann, T. (2015). Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration. Journal of Neuroinflammation 12, 209; doi:10.1186/s12974-015-0431-4.CrossRefGoogle ScholarPubMed
Stone, J. & Dreher, Z. (1987). Relationship between astrocytes, ganglion cells and vasculature of the retina. Journal of Comparative Neurology 255, 35–49.CrossRefGoogle ScholarPubMed
Streit, W.J. (2002). Microglia as neuroprotective, immunocompetent cells of the CNS. GLIA 40, 133–139; doi:10.1002/glia.10154.CrossRefGoogle ScholarPubMed
Telegina, D.V., Kozhevnikova, O.S. & Kolosova, N.G. (2018). Changes in retinal glial cells with age and during development of age-related macular degeneration. Biochemistry (Moscow) 83, 1009–1017; doi:10.1134/S000629791809002X.CrossRefGoogle ScholarPubMed
Vecino, E., Rodriguez, F.D., Ruzafa, N., Pereiro, X. & Sharma, S.C. (2016). Glia-neuron interactions in the mammalian retina. Progress in Retinal and Eye Research 51, 1–40; doi:10.1016/j.preteyeres.2015.06.003.CrossRefGoogle ScholarPubMed
Wang, S.K. & Cepko, C.L. (2022). Targeting microglia to treat degenerative eye diseases. Frontiers in Immunology 13, 843558; doi:10.3389/fimmu.2022.843558.CrossRefGoogle ScholarPubMed
Wu, J., Seregard, S. & Algvere, P.V. (2006). Photochemical damage of the retina. Survey of Ophthalmology 51, 461–481.CrossRefGoogle ScholarPubMed
Yang, Z. & Wang, K.K.W. (2015). Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker. Trends in Neurosciences 38, 364–374; doi:10.1016/j.tins.2015.04.003.CrossRefGoogle ScholarPubMed
Yang, L.P., Zhu, X.A. & Tso, M.O.M. (2007). A possible mechanism of microglia-photoreceptor crosstalk. Molecular Vision 13, 2048–2057.Google ScholarPubMed
Zhang, C., Shen, J.K., Lam, T.T., Zeng, H.Y., Chiang, S.K., Yang, F. & Tso, M.O.M. (2005). Activation of microglia and chemokines in light-induced retinal degeneration. Molecular Vision 11, 887–895.Google ScholarPubMed
Zhang, M., Xu, G., Liu, W., Ni, Y. & Zhou, W. (2012). Role of fractalkine/CX3CR1 interaction in light-induced photoreceptor degeneration through regulating retinal microglial activation and migration. PLoS One 7, e35446; doi:10.1371/journal.pone.0035446.CrossRefGoogle ScholarPubMed