Abstract
While light is the basic element for inducing vision and modulating circadian rhythms, excessive light has been reported to have a negative effect on the survival of various types of retinal cells. Among them photoreceptors and retinal pigment epithelial (RPE) cells degeneration after light exposure is widely observed, but light-induced retinal ganglion cell (RGC) damage achieves relatively little attention. The purpose of this article is to summarize the experimental evidence for the possible negative effects of excessive light on RGCs. By searching the database, twenty-six related articles have been included. Taken together, excessive light may insult RGCs through the three main ways: (i) directly action on RGC mitochondria, as well as DNA, resulting in an upregulation of reactive oxygen species (ROS) and subsequently caspase-dependent or -independent cell death; (ii) mediation in gliotransmitters or relevant receptors of retinal glial cells; and (iii) a secondary event to photoreceptors and RPE cells degeneration and subsequent retinal remodeling. So RGCs can certainly be injured by excessive light, especially when they are already energetically compromised in some diseases. And more attentions should be paid to this topic to take timely measures to protect these frail RGCs from being damaged by excessive light.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Boulton M, Rozanowska M, Rozanowski B (2001) Retinal photodamage. J Photochem Photobiol B 64(2–3):144–161. https://doi.org/10.1016/s1011-1344(01)00227-5
Carelli V, Ross-Cisneros FN, Sadun AA (2004) Mitochondrial dysfunction as a cause of optic neuropathies. Prog Retin Eye Res 23(1):53–89. https://doi.org/10.1016/j.preteyeres.2003.10.003
Chen SK, Badea TC, Hattar S (2011) Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs. Nature 476(7358):92–95. https://doi.org/10.1038/nature10206
Cideciyan AV, Hood DC, Huang Y, Banin E, Li ZY, Stone EM, Milam AH, Jacobson SG (1998) Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man. Proc Natl Acad Sci USA 95(12):7103–7108. https://doi.org/10.1073/pnas.95.12.7103
Dai M, Liu Y, Nie X, Zhang J, Wang Y, Ben J, Zhang S, Yang X, Sang A (2015) Expression of RBMX in the light-induced damage of rat retina in vivo. Cell Mol Neurobiol 35(4):463–471. https://doi.org/10.1007/s10571-014-0140-z
Del Olmo-Aguado S, Manso AG, Osborne NN (2012) Light might directly affect retinal ganglion cell mitochondria to potentially influence function. Photochem Photobiol 88(6):1346–1355. https://doi.org/10.1111/j.1751-1097.2012.01120.x
Del Olmo-Aguado S, Nunez-Alvarez C, Ji D, Manso AG, Osborne NN (2013) RTP801 immunoreactivity in retinal ganglion cells and its down-regulation in cultured cells protect them from light and cobalt chloride. Brain Res Bull 98:132–144. https://doi.org/10.1016/j.brainresbull.2013.08.002
Del Olmo-Aguado S, Nunez-Alvarez C, Osborne NN (2016a) Blue light action on mitochondria leads to cell death by necroptosis. Neurochem Res 41(9):2324–2335. https://doi.org/10.1007/s11064-016-1946-5
Del Olmo-Aguado S, Nunez-Alvarez C, Osborne NN (2016b) Red light of the visual spectrum attenuates cell death in culture and retinal ganglion cell death in situ. Acta Ophthalmol 94(6):e481–491. https://doi.org/10.1111/aos.12996
Feng J, Chen Y, Lu B, Sun X, Zhu H, Sun X (2019) Autophagy activated via GRP78 to alleviate endoplasmic reticulum stress for cell survival in blue light-mediated damage of A2E-laden RPEs. BMC Ophthalmol 19(1):249. https://doi.org/10.1186/s12886-019-1261-4
Frassetto LJ, Schlieve CR, Lieven CJ, Utter AA, Jones MV, Agarwal N, Levin LA (2006) Kinase-dependent differentiation of a retinal ganglion cell precursor. Invest Ophthalmol Vis Sci 47(1):427–438. https://doi.org/10.1167/iovs.05-0340
Ganapathy PS, Dun Y, Ha Y, Duplantier J, Allen JB, Farooq A, Bozard BR, Smith SB (2010) Sensitivity of staurosporine-induced differentiated RGC-5 cells to homocysteine. Curr Eye Res 35(1):80–90. https://doi.org/10.3109/02713680903421194
Garcia-Ayuso D, Salinas-Navarro M, Agudo-Barriuso M, Alarcon-Martinez L, Vidal-Sanz M, Villegas-Perez MP (2011) Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration. Mol Vis 17:1716–1733
Garcia-Ayuso D, Galindo-Romero C, Di Pierdomenico J, Vidal-Sanz M, Agudo-Barriuso M, Villegas Perez MP (2017) Light-induced retinal degeneration causes a transient downregulation of melanopsin in the rat retina. Exp Eye Res 161:10–16. https://doi.org/10.1016/j.exer.2017.05.010
Garcia-Ayuso D, Di Pierdomenico J, Agudo-Barriuso M, Vidal-Sanz M, Villegas-Perez MP (2018) Retinal remodeling following photoreceptor degeneration causes retinal ganglion cell death. Neural Regen Res 13(11):1885–1886. https://doi.org/10.4103/1673-5374.239436
Garcia-Ayuso D, Di Pierdomenico J, Vidal-Sanz M, Villegas-Perez MP (2019) Retinal ganglion cell death as a late remodeling effect of photoreceptor degeneration. Int J Mol Sci 20:18. https://doi.org/10.3390/ijms20184649
Hu Y (2016) Axon injury induced endoplasmic reticulum stress and neurodegeneration. Neural Regen Res 11(10):1557–1559. https://doi.org/10.4103/1673-5374.193225
Huang C, Zhang P, Wang W, Xu Y, Wang M, Chen X, Dong X (2014) Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways. Apoptosis 19(6):922–932. https://doi.org/10.1007/s10495-014-0983-2
Iandiev I, Wurm A, Hollborn M, Wiedemann P, Grimm C, Reme CE, Reichenbach A, Pannicke T, Bringmann A (2008) Muller cell response to blue light injury of the rat retina. Invest Ophthalmol Vis Sci 49(8):3559–3567. https://doi.org/10.1167/iovs.08-1723
Ji D, Kamalden TA, del Olmo-Aguado S, Osborne NN (2011) Light- and sodium azide-induced death of RGC-5 cells in culture occurs via different mechanisms. Apoptosis 16(4):425–437. https://doi.org/10.1007/s10495-011-0574-4
Jou MJ, Jou SB, Guo MJ, Wu HY, Peng TI (2004) Mitochondrial reactive oxygen species generation and calcium increase induced by visible light in astrocytes. Ann N Y Acad Sci 1011:45–56. https://doi.org/10.1007/978-3-662-41088-2_5
Karu TI, Pyatibrat LV, Kalendo GS (2004) Photobiological modulation of cell attachment via cytochrome c oxidase. Photochem Photobiol Sci 3(2):211–216. https://doi.org/10.1039/b306126d
Kaufman RJ (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13(10):1211–1233. https://doi.org/10.1101/gad.13.10.1211
Krinsky NI, Landrum JT, Bone RA (2003) Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr 23:171–201. https://doi.org/10.1146/annurev.nutr.23.011702.073307
Krishnamoorthy RR, Agarwal P, Prasanna G, Vopat K, Lambert W, Sheedlo HJ, Pang IH, Shade D, Wordinger RJ, Yorio T, Clark AF, Agarwal N (2001) Characterization of a transformed rat retinal ganglion cell line. Brain Res Mol Brain Res 86(1–2):1–12. https://doi.org/10.1016/s0169-328x(00)00224-2
Lascaratos G, Ji D, Wood JP, Osborne NN (2007) Visible light affects mitochondrial function and induces neuronal death in retinal cell cultures. Vision Res 47(9):1191–1201. https://doi.org/10.1016/j.visres.2006.12.014
LeGates TA, Fernandez DC, Hattar S (2014) Light as a central modulator of circadian rhythms, sleep and affect. Nat Rev Neurosci 15(7):443–454. https://doi.org/10.1038/nrn3743
Li GY, Osborne NN (2008) Oxidative-induced apoptosis to an immortalized ganglion cell line is caspase independent but involves the activation of poly(ADP-ribose)polymerase and apoptosis-inducing factor. Brain Res 1188:35–43. https://doi.org/10.1016/j.brainres.2007.10.073
Li GY, Fan B, Ma TH (2011) Visible light may directly induce nuclear DNA damage triggering the death pathway in RGC-5 cells. Mol Vis 17:3279–3289
Lin CI, Chiao CC (2019) Blue light promotes neurite outgrowth of retinal explants in postnatal ChR2 mice. ENeuro 6:4. https://doi.org/10.1523/ENEURO.0391-18.2019
Liu L, Wu J, Zhou X, Chen Z, Zhou G (2012) The impact of visible light on the immature retina: a model of early light exposure in neonatal mice. Brain Res Bull 87(6):534–539. https://doi.org/10.1016/j.brainresbull.2012.02.009
Liu X, Yang X, Zhu R, Dai M, Zhu M, Shen Y, Fang H, Sang A, Chen H (2017) Involvement of Fra-1 in retinal ganglion cell apoptosis in rat light-induced retina damage model. Cell Mol Neurobiol 37(1):83–92. https://doi.org/10.1007/s10571-016-0346-3
Moorhouse AJ, Li S, Vickery RM, Hill MA, Morley JW (2004) A patch-clamp investigation of membrane currents in a novel mammalian retinal ganglion cell line. Brain Res 1003(1–2):205–208. https://doi.org/10.1016/j.brainres.2004.01.027
Munoz MA, Pacheco A, Becker MI, Silva E, Ebensperger R, Garcia AM, De Ioannes AE, Edwards AM (2011) Different cell death mechanisms are induced by a hydrophobic flavin in human tumor cells after visible light irradiation. J Photochem Photobiol B 103(1):57–67. https://doi.org/10.1016/j.jphotobiol.2011.01.012
Nakanishi T, Shimazawa M, Sugitani S, Kudo T, Imai S, Inokuchi Y, Tsuruma K, Hara H (2013) Role of endoplasmic reticulum stress in light-induced photoreceptor degeneration in mice. J Neurochem 125(1):111–124. https://doi.org/10.1111/jnc.12116
Newman EA (2015) Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters. Philos Trans R Soc Lond B 370:1672. https://doi.org/10.1098/rstb.2014.0195
Organisciak DT, Vaughan DK (2010) Retinal light damage: mechanisms and protection. Prog Retin Eye Res 29(2):113–134. https://doi.org/10.1016/j.preteyeres.2009.11.004
Ortiz MPR (1995) The 1994 Bernard B Brodie Award Lecture Structure, mechanism, and inhibition of cytochrome P450. Drug Metab Dispos 23(11):1181–1187
Osborne NN, Lascaratos G, Bron AJ, Chidlow G, Wood JP (2006) A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies. Br J Ophthalmol 90(2):237–241. https://doi.org/10.1136/bjo.2005.082230
Osborne NN, Li GY, Ji D, Mortiboys HJ, Jackson S (2008) Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies. J Neurochem 105(5):2013–2028. https://doi.org/10.1111/j.1471-4159.2008.05320.x
Osborne NN, Nunez-Alvarez C, Del Olmo-Aguado S (2014) The effect of visual blue light on mitochondrial function associated with retinal ganglions cells. Exp Eye Res 128:8–14. https://doi.org/10.1016/j.exer.2014.08.012
Osborne NN, Nunez-Alvarez C, Del Olmo-Aguado S, Merrayo-Lloves J (2017) Visual light effects on mitochondria: the potential implications in relation to glaucoma. Mitochondrion 36:29–35. https://doi.org/10.1016/j.mito.2016.11.009
Peters JC, Bhattacharya S, Clark AF, Zode GS (2015) Increased endoplasmic reticulum stress in human glaucomatous trabecular meshwork cells and tissues. Invest Ophthalmol Vis Sci 56(6):3860–3868. https://doi.org/10.1167/iovs.14-16220
Sang A, Cheng Y, Lu H, Chen D, Gao R, Shen A (2011) Light-induced retinal ganglion cell damage in vivo involves Dexras1. Mol Vis 17:134–143
Sang A, Xu Y, Jin N, Zhou T, Wang J, Zhu J, Chen C, Shi J, Shuai J, Xu G, Gu Z (2013) Involvement of transcription initiation factor IIB in the light-induced death of rat retinal ganglion cells in vivo. J Mol Histol 44(1):11–18. https://doi.org/10.1007/s10735-012-9446-7
Sang A, Yang X, Chen H, Qin B, Zhu M, Dai M, Zhu R, Liu X (2015) Upregulation of SYF2 relates to retinal ganglion cell apoptosis and retinal glia cell proliferation after light-induced retinal damage. J Mol Neurosci 56(2):480–490. https://doi.org/10.1007/s12031-015-0534-5
Schmidt TM, Chen SK, Hattar S (2011) Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci 34(11):572–580. https://doi.org/10.1016/j.tins.2011.07.001
Shu Q, Xu Y, Zhuang H, Fan J, Sun Z, Zhang M, Xu G (2014) Ras homolog enriched in the brain is linked to retinal ganglion cell apoptosis after light injury in rats. J Mol Neurosci 54(2):243–251. https://doi.org/10.1007/s12031-014-0281-z
Simons K (1993) Artificial light and early-life exposure in age-related macular degeneration and in cataractogenic phototoxicity. Arch Ophthalmol 111(3):297–298. https://doi.org/10.1001/archopht.1993.01090030015002
Thanos S, Heiduschka P, Romann I (2001) Exposure to a solar eclipse causes neuronal death in the retina. Graefes Arch Clin Exp Ophthalmol 239(10):794–800. https://doi.org/10.1007/s004170100362
Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS, Walter P (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101(3):249–258. https://doi.org/10.1016/s0092-8674(00)80835-1
Van Bergen NJ, Wood JP, Chidlow G, Trounce IA, Casson RJ, Ju WK, Weinreb RN, Crowston JG (2009) Recharacterization of the RGC-5 retinal ganglion cell line. Invest Ophthalmol Vis Sci 50(9):4267–4272. https://doi.org/10.1167/iovs.09-3484
Wahlin KJ, Campochiaro PA, Zack DJ, Adler R (2000) Neurotrophic factors cause activation of intracellular signaling pathways in Muller cells and other cells of the inner retina, but not photoreceptors. Invest Ophthalmol Vis Sci 41(3):927–936
Wasowicz M, Morice C, Ferrari P, Callebert J, Versaux-Botteri C (2002) Long-term effects of light damage on the retina of albino and pigmented rats. Invest Ophthalmol Vis Sci 43(3):813–820
Wenzel A, Grimm C, Samardzija M, Reme CE (2005) Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res 24(2):275–306. https://doi.org/10.1016/j.preteyeres.2004.08.002
Wood JP, Chidlow G, Graham M, Osborne NN (2005) Energy substrate requirements for survival of rat retinal cells in culture: the importance of glucose and monocarboxylates. J Neurochem 93(3):686–697. https://doi.org/10.1111/j.1471-4159.2005.03059.x
Wood JP, Lascaratos G, Bron AJ, Osborne NN (2007) The influence of visible light exposure on cultured RGC-5 cells. Mol Vis 14:334–344
Wood JP, Chidlow G, Tran T, Crowston JG, Casson RJ (2010) A comparison of differentiation protocols for RGC-5 cells. Invest Ophthalmol Vis Sci 51(7):3774–3783. https://doi.org/10.1167/iovs.09-4305
Xu Y, Yang L, Yu S, Shu Q, Yang C, Wang J, Xu F, Sang A, Liang X (2014a) Spatiotemporal changes in NFATc4 expression of retinal ganglion cells after light-induced damage. J Mol Neurosci 53(1):69–77. https://doi.org/10.1007/s12031-013-0198-y
Xu Y, Yu S, Shu Q, Yang L, Yang C, Wang J, Xu F, Ji M, Liang X (2014b) Upregulation of CREM-1 relates to retinal ganglion cells apoptosis after light-induced damage in vivo. J Mol Neurosci 52(3):331–338. https://doi.org/10.1007/s12031-013-0153-y
Yang LP, Wu LM, Guo XJ, Li Y, Tso MO (2008) Endoplasmic reticulum stress is activated in light-induced retinal degeneration. J Neurosci Res 86(4):910–919. https://doi.org/10.1002/jnr.21535
Yang X, Chen H, Zhu M, Zhu R, Qin B, Fang H, Dai M, Sang A, Liu X (2015) Up-regulation of PKM2 relates to retinal ganglion cell apoptosis after light-induced retinal damage in adult rats. Cell Mol Neurobiol 35(8):1175–1186. https://doi.org/10.1007/s10571-015-0211-9
Zhang P, Huang C, Wang W, Wang M (2015) Early changes in staurosporine-induced differentiated RGC-5 cells indicate cellular injury response to nonlethal blue light exposure. Photochem Photobiol Sci 14(6):1093–1099. https://doi.org/10.1039/c4pp00456f
Funding
Funding was provided by National Health and Family Planning Commission of China (WKJ-ZJ-1820) and Department of Science and Technology of Zhejiang Province (2018C03017).
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhao, Y., Shen, Y. Light-Induced Retinal Ganglion Cell Damage and the Relevant Mechanisms. Cell Mol Neurobiol 40, 1243–1252 (2020). https://doi.org/10.1007/s10571-020-00819-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-020-00819-0