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Abstract:

Non-exudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. The macular retinal pigment epithelium (RPE) lies in a high oxidative environment because its high metabolic demand, mitochondria concentration, reactive oxygen species levels, and macular blood flow. It has been suggested that oxidative stress-induced damage to the RPE plays a key role in NE-AMD pathogenesis. The fact that the disease limits to the macular region raises the question as to why this area is particularly susceptible. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks exclusively circumscribed to the temporal region of the RPE/outer retina. The aim of this work was analyzing RPE regional differences that could explain AMD localized susceptibility. Lower melanin content, thicker basal infoldings, higher mitochondrial mass, and higher levels of antioxidant enzymes, were found in the temporal RPE compared with the nasal region. Moreover, SCGx induced a decrease in the antioxidant system, and in mitochondria mass, as well as an increase in mitochondria superoxide, lipid peroxidation products, nuclear Nrf2 and heme oxygenase-1 levels, and in the occurrence of damaged mitochondria exclusively at the temporal RPE. These findings suggest that despite the well-known differences between the human and mouse retina, it might not be NE-AMD pathophysiology which conditions the localization of the disease, but the macular RPE histologic and metabolic specific attributes that make it more susceptible to choroid alterations leading initially to a localized RPE dysfunction/damage, and secondarily to macular degeneration. © 2018 Elsevier Inc.

Registro:

Documento: Artículo
Título:Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration
Autor:Dieguez, H.H.; Romeo, H.E.; Alaimo, A.; González Fleitas, M.F.; Aranda, M.L.; Rosenstein, R.E.; Dorfman, D.
Filiación:Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine/CEFyBO, University of Buenos Aires/CONICET, Buenos Aires, Argentina
School of Engineering and Agrarian Sciences, Pontifical Catholic University of Argentina, BIOMED/UCA/CONICET, Buenos Aires, Argentina
Interdisciplinary Laboratory of Cellular Dynamics and Nanotools, Department of Biological Chemistry, Faculty of Exact and Natural Sciences/IQUIBICEN, University of Buenos Aires/CONICET, Buenos Aires, Argentina
Palabras clave:Antioxidant system; Mitochondria; Non-exudative age-related macular degeneration; Oxidative stress; Retinal pigment epithelium; Superior cervical ganglion; catalase; copper zinc superoxide dismutase; glutathione peroxidase; heme oxygenase 1; manganese superoxide dismutase; melanin; superoxide; transcription factor Nrf2; adult; age related macular degeneration; animal experiment; animal model; animal tissue; antioxidant activity; Article; C57BL 6 mouse; cell nucleus; cellular parameters; controlled study; disorders of mitochondrial functions; enzyme activity; histopathology; lipid peroxidation; male; mitochondrial mass; mouse; non exudative age related macular degeneration; nonhuman; oxidative stress; pathophysiology; priority journal; protein analysis; retina pigment epitheliopathy; retinal outer nuclear layer; retinal pigment epithelium; superior cervical ganglionectomy
Año:2019
Volumen:131
Página de inicio:72
Página de fin:80
DOI: http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.035
Título revista:Free Radical Biology and Medicine
Título revista abreviado:Free Radic. Biol. Med.
ISSN:08915849
CODEN:FRBME
CAS:catalase, 9001-05-2; copper zinc superoxide dismutase, 149394-67-2; glutathione peroxidase, 9013-66-5; melanin, 8049-97-6; superoxide, 11062-77-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08915849_v131_n_p72_Dieguez

Referencias:

  • Ach, T., Tolstik, E., Messinger, J.D., Zarubina, A.V., Heintzmann, R., Curcio, C.A., Lipofuscin redistribution and loss accompanied by cytoskeletal stress in retinal pigment epithelium of eyes with age-related macular degeneration (2015) Investig. Ophthalmol. Vis. Sci., 56, pp. 3242-3252
  • Bowes Rickman, C., Farsiu, S., Toth, C.A., Klingeborn, M., Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging (2013) Invest Ophthalmol. Vis. Sci., 54. , (ORSF68-80)
  • Brown, E.E., Lewin, A.S., Ash, J.D., Mitochondria: potential Targets for Protection in Age-Related Macular Degeneration (2018) Adv. Exp. Med. Biol., 1074, pp. 11-17
  • Buschini, E., Fea, A.M., Lavia, C.A., Nassisi, M., Pignata, G., Zola, M., Grignolo, F.M., Recent developments in the management of dry age-related macular degeneration (2015) Clin. Ophthalmol., 9, pp. 563-574
  • Cai, J., Nelson, K.C., Wu, M., Sternberg, P., Jr, Jones, D.P., Oxidative damage and protection of the RPE (2000) Prog. Retin. Eye Res., 19, pp. 205-221
  • Datta, S., Cano, M., Ebrahimi, K., Wang, L., Handa, J.T., The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD (2017) Prog. Retin. Eye Res., 60, pp. 201-218
  • Dieguez, H.H., Romeo, H.E., González Fleitas, M.F., Aranda, M.L., Milne, G.A., Rosenstein, R.E., Dorfman, D., Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice (2018) Dis. Model Mech., 11 (2). , (pii: dmm031641)
  • Ding, X., Patel, M., Chan, C.C., Molecular pathology of age-related macular degeneration (2009) Prog. Retin. Eye Res., 28, pp. 1-18
  • Durairaj, C., Chastain, J.E., Kompella, U.B., Intraocular distribution of melanin in human, monkey, rabbit, minipig and dog eyes (2012) Exp. Eye Res., 98, pp. 23-27
  • Feher, J., Kovacs, I., Artico, M., Cavallotti, C., Papale, A., Balacco Gabrieli, C., Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration (2006) Neurobiol. Aging, 27, pp. 983-993
  • Golestaneh, N., Chu, Y., Xiao, Y.Y., Stoleru, G.L., Theos, A.C., Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration (2017) Cell Death Dis., 8, p. e2537
  • Jager, R.D., Mieler, W.F., Miller, J.W., Age-related macular degeneration (2008) N. Engl. J. Med., 358, pp. 2606-2617
  • Hanus, J., Anderson, C., Wang, S., RPE necroptosis in response to oxidative stress and in AMD (2015) Ageing Res. Rev., 24, pp. 286-298
  • Hyttinen, J.M.T., Viiri, J., Kaarniranta, K., Błasiak, J., Mitochondrial quality control in AMD: does mitophagy play a pivotal role? (2018) Cell Mol. Life Sci.
  • Karunadharma, P.P., Nordgaard, C.L., Olsen, T.W., Ferrington, D.A., Mitochondrial DNA damage as a potential mechanism for age-related macular degeneration (2010) Investig. Ophthalmol. Vis. Sci., 51, pp. 5470-5479
  • Laboda, A., Damulewicz, M., Pyza, E., Jozkowicz, A., Dulak, J., Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism (2016) Cell Mol. Life Sci., 17, pp. 3221-3247
  • Lambert, N.G., ElShelmani, H., Singh, M.K., Mansergh, F.C., Wride, M.A., Padilla, M., Keegan, D., Ambati, B.K., Risk factors and biomarkers of age-related macular degeneration (2016) Prog. Retin. Eye Res., 54, pp. 64-102
  • Lambros, M.L., Plafker, S.M., Oxidative stress and the Nrf2 anti-oxidant transcription factor in age-related macular degeneration (2016) Adv. Exp. Med. Biol., 854, pp. 67-72
  • Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., Protein measurement with the Folin phenol reagent (1951) J. Biol. Chem., 193, pp. 265-275
  • Mao, H., Seo, S.J., Biswal, M.R., Li, H., Conners, M., Nandyala, A., Jones, K., Lewin, A.S., Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration (2014) Investig. Ophthalmol. Vis. Sci., 55, pp. 4613-4627
  • McCord, J.M., Edeas, M.A., SOD, oxidative stress and human pathologies: a brief history and a future vision (2005) Biomed. Pharmacother., 59, pp. 139-142
  • Romeo, H.E., Colombo, L.L., Esquifino, A.I., Rosenstein, R.E., Chuluyan, H.E., Cardinali, D.P., Slower growth of tumours in sympathetically denervated murine skin (1991) J. Auton. Nerv. Syst., 32, pp. 159-164
  • Sachdeva, M.M., Cano, M., Handa, J.T., Nrf2 signaling is impaired in the aging RPE given an oxidative insult (2014) Exp. Eye Res., 119, pp. 111-114
  • Schmidt, S.Y., Peisch, R.D., Melanin concentration in normal human retinal pigment epithelium. Regional variation and age-related reduction (1986) Investig. Ophthalmol. Vis. Sci., 27, pp. 1063-1067
  • Terluk, M.R., Kapphahn, R.J., Soukup, L.M., Gong, H., Gallardo, C., Montezuma, S.R., Ferrington, D.A., Investigating mitochondria as a target for treating age-related macular degeneration (2015) J. Neurosci., 35, pp. 7304-7311
  • van Lookeren Campagne, M., LeCouter, J., Yaspan, B.L., Ye, W., Mechanisms of age-related macular degeneration and therapeutic opportunities (2014) J. Pathol., 232, pp. 151-164
  • Van Remmen, H., Richardson, A., Oxidative damage to mitochondria and aging (2001) Exp. Gerontol., 36, pp. 957-968
  • Volland, S., Esteve-Rudd, J., Hoo, J., Yee, C., Williams, D.S., A comparison of some organizational characteristics of the mouse central retina and the human macula (2015) PLoS One, 10, p. e0125631
  • Winkler, B.S., Boulton, M.E., Gottsch, J.D., Sternberg, P., Oxidative damage and age-related macular degeneration (1999) Mol. Vis., 5, pp. 32-58
  • Wong, W.L., Su, X., Li, X., Cheung, C.M., Klein, R., Cheng, C.Y., Wong, T.Y., Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis (2014) Lancet Glob. Health, 2, pp. 106-116
  • Zarbin, M.A., Current concepts in the pathogenesis of age-related macular degeneration (2004) Arch. Ophthalmol., 122, pp. 598-614
  • Zhao, C., Yasumura, D., Li, X., Matthes, M., Lloyd, M., Nielsen, G., Ahern, K., Vollrath, D., mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice (2011) J. Clin. Investig., 121, pp. 369-383

Citas:

---------- APA ----------
Dieguez, H.H., Romeo, H.E., Alaimo, A., González Fleitas, M.F., Aranda, M.L., Rosenstein, R.E. & Dorfman, D. (2019) . Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration. Free Radical Biology and Medicine, 131, 72-80.
http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.035
---------- CHICAGO ----------
Dieguez, H.H., Romeo, H.E., Alaimo, A., González Fleitas, M.F., Aranda, M.L., Rosenstein, R.E., et al. "Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration" . Free Radical Biology and Medicine 131 (2019) : 72-80.
http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.035
---------- MLA ----------
Dieguez, H.H., Romeo, H.E., Alaimo, A., González Fleitas, M.F., Aranda, M.L., Rosenstein, R.E., et al. "Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration" . Free Radical Biology and Medicine, vol. 131, 2019, pp. 72-80.
http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.035
---------- VANCOUVER ----------
Dieguez, H.H., Romeo, H.E., Alaimo, A., González Fleitas, M.F., Aranda, M.L., Rosenstein, R.E., et al. Oxidative stress damage circumscribed to the central temporal retinal pigment epithelium in early experimental non-exudative age-related macular degeneration. Free Radic. Biol. Med. 2019;131:72-80.
http://dx.doi.org/10.1016/j.freeradbiomed.2018.11.035