Immunohistochemical and ultrastructural analysis revealed signs of structural alterations in neurons and autophagy in all layers of the human retina at the end-stage glaucoma. The most pronounced destructive changes associated with swelling and destruction of mitochondria, endoplasmic reticulum, and Golgi apparatus, as well as structural signs of impaired synaptic activity and apoptosis were noted in ganglion, bipolar, and amacrine neurons. In the structure of photoreceptor cells, alone with destructive processes associated with structural alterations of rods and cones in the outer membrane discs, as well as swelling of organelles, we observed processes aimed at the maintenance of cell homeostasis. Structural signs of autophagy (mainly mitophagy) and changes of the ultrastructural organization in rod neurons were more pronounced than in cones.
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Adornetto A, Parisi V, Morrone LA, Corasaniti MT, Bagetta G, Tonin P, Russo R. The role of autophagy in glaucomatous optic neuropathy. Front. Cell Dev. Biol. 2020;8:121. doi: https://doi.org/10.3389/fcell.2020.00121
Andres-Alonso M, Kreutz MR, Karpova A. Autophagy and the endolysosomal system in presynaptic function. Cell. Mol. Life Sci. 2021;78(6):2621-2639. doi: https://doi.org/10.1007/s00018-020-03722-5
Cai Q, Jeong YY. Mitophagy in Alzheimer’s disease and other age-related neurodegenerative diseases. Cells. 2020;9(1):150. doi: https://doi.org/10.3390/cells9010150
He JN, Zhang SD, Qu Y, Wang HL, Tham CC, Pang CP, Chu WK. Rapamycin removes damaged mitochondria and protects human trabecular meshwork (TM-1) cells from chronic oxidative stress. Mol. Neurobiol. 2019;56(9):6586-6593. doi: https://doi.org/10.1007/s12035-019-1559-5
He S, Stankowska DL, Ellis DZ, Krishnamoorthy RR, Yorio T. Targets of Neuroprotection in Glaucoma. J. Ocul. Pharmacol. Ther. 2018;34(1-2):85-106. doi: https://doi.org/10.1089/jop.2017.0041
Koch JC, Lingor P. The role of autophagy in axonal degeneration of the optic nerve. Exp. Eye Res. 2016;144:81-89. doi: https://doi.org/10.1016/j.exer.2015.08.016
Liang Y. Emerging concepts and functions of autophagy as a regulator of synaptic components and plasticity. Cells. 2019;8(1):34. doi: https://doi.org/10.3390/cells8010034
McMonnies C. Reactive oxygen species, oxidative stress, glaucoma and hyperbaric oxygen therapy. J. Optom. 2018;11(1):3-9. doi: https://doi.org/10.1016/j.optom.2017.06.002
Munemasa Y, Kitaoka Y. Autophagy in axonal degeneration in glaucomatous optic neuropathy. Prog. Retin. Eye Res. 2015;47:1-18. doi: https://doi.org/10.1016/j.preteyeres.2015.03.002
Muniz-Feliciano L, Doggett TA, Zhou Z, Ferguson TA. RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye. Autophagy. 2017;13(12):2072-2085. doi: https://doi.org/10.1080/15548627.2017.1380124
Nettesheim A, Dixon A, Shim MS, Coyne A, Walsh M, Liton PB. Autophagy in the aging and experimental ocular hypertensive mouse model. Invest. Ophthalmol. Vis. Sci. 2020;61(10):31. doi: https://doi.org/10.1167/iovs.61.10.31
Overhoff M, De Bruyckere E, Kononenko NL. Mechanisms of neuronal survival safeguarded by endocytosis and autophagy. J. Neurochem. 2021;157(2):263-296. doi: https://doi.org/10.1111/jnc.15194
Seo S, Datta P. Photoreceptor outer segment as a sink for membrane proteins: hypothesis and implications in retinal ciliopathies. Hum. Mol. Genet. 2017;26(R1):R75-R82. doi: https://doi.org/10.1093/hmg/ddx163
Stothert AR, Fontaine SN, Sabbagh JJ, Dickey CA. Targeting the ER-autophagy system in the trabecular meshwork to treat glaucoma. Exp. Eye Res. 2016;144:38-45. doi: https://doi.org/10.1016/j.exer.2015.08.017
Zaffagnini G, Martens S. Mechanisms of selective autophagy. J. Mol. Biol. 2016;428(9, Pt A):1714-1724. doi: 10.1016/j.jmb.2016.02.004
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 173, No. 4, pp. 479-485, April, 2022
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Obanina, N.A., Bgatova, N.P., Eremina, A.V. et al. Autophagy in Human Retinal Neurons in Glaucoma. Bull Exp Biol Med 173, 468–474 (2022). https://doi.org/10.1007/s10517-022-05563-7
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DOI: https://doi.org/10.1007/s10517-022-05563-7