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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Editorial

Curcumin as a Perspective Protection for Retinal Pigment Epithelium during Autophagy Inhibition in the Course of Retinal Degeneration

Author(s): Roberto Pinelli, Michela Ferrucci, Francesca Biagioni, Violet Bumah, Elena Scaffidi, Stefano Puglisi-Allegra and Francesco Fornai*

Volume 21, Issue 11, 2023

Published on: 05 July, 2023

Page: [2227 - 2232] Pages: 6

DOI: 10.2174/1570159X21666230705103839

Price: $65

Abstract

Defective autophagy in the retinal pigment epithelium (RPE) is involved in retinal degeneration, mostly in the course of age-related macular degeneration (AMD), which is an increasingly prevalent retinal disorder, eventually leading to blindness. However, most autophagy activators own serious adverse effects when administered systemically. Curcumin is a phytochemical, which induces autophagy with a wide dose-response curve, which brings minimal side effects. Recent studies indicating defective autophagy in AMD were analyzed. Accordingly, in this perspective, we discuss and provide some evidence about the protective effects of curcumin in preventing RPE cell damage induced by the autophagy inhibitor 3-methyladenine (3-MA). Cells from human RPE were administered the autophagy inhibitor 3-MA. The cell damage induced by 3-MA was assessed at light microscopy by hematoxylin & eosin, Fluoro Jade-B, and ZO1 immunohistochemistry along with electron microscopy. The autophagy inhibitor 3-MA produces cell loss and cell degeneration of RPE cells. These effects are counteracted dose-dependently by curcumin. In line with the hypothesis that the autophagy machinery is key in sustaining the integrity of the RPE, here we provide evidence that the powerful autophagy inhibitor 3-MA produces dose-dependently cell loss and cell degeneration in cultured RPE cells, while inhibiting autophagy as shown by LC3-II/LC3-I ratio and gold-standard assessment of autophagy through LC3-positive autophagy vacuoles. These effects are prevented dose-dependently by curcumin, which activates autophagy. These data shed the perspective of validating the role of phytochemicals as safe autophagy activators to treat AMD.

[1]
Bento, C.F.; Renna, M.; Ghislat, G.; Puri, C.; Ashkenazi, A.; Vicinanza, M.; Menzies, F.M.; Rubinsztein, D.C. Mammalian autophagy: How does it work? Annu. Rev. Biochem., 2016, 85(1), 685-713.
[http://dx.doi.org/10.1146/annurev-biochem-060815-014556] [PMID: 26865532]
[2]
Klionsky, D.J.; Codogno, P. The mechanism and physiological function of macroautophagy. J. Innate Immun., 2013, 5(5), 427-433.
[http://dx.doi.org/10.1159/000351979] [PMID: 23774579]
[3]
Pinelli, R.; Biagioni, F.; Limanaqi, F.; Bertelli, M.; Scaffidi, E.; Polzella, M.; Busceti, C.L.; Fornai, F. A re-appraisal of pathogenic mechanisms bridging wet and dry age-related macular degeneration leads to reconsider a role for phytochemicals. Int. J. Mol. Sci., 2020, 21(15), 5563.
[http://dx.doi.org/10.3390/ijms21155563] [PMID: 32756487]
[4]
Lewis Luján, L.M.; McCarty, M.F.; Di Nicolantonio, J.J.; Gálvez Ruiz, J.C.; Rosas-Burgos, E.C.; Plascencia-Jatomea, M.; Iloki Assanga, S.B. Nutraceuticals/drugs promoting mitophagy and mitochondrial biogenesis may combat the mitochondrial dysfunction driving progression of dry age-related macular degeneration. Nutrients, 2022, 14(9), 1985.
[http://dx.doi.org/10.3390/nu14091985] [PMID: 35565950]
[5]
Kaarniranta, K.; Blasiak, J.; Liton, P.; Boulton, M.; Klionsky, D.J.; Sinha, D. Autophagy in age-related macular degeneration. Autophagy, 2022, 19(2), 388-400.
[http://dx.doi.org/10.1080/15548627.2022.2069437] [PMID: 35468037]
[6]
Bergen, A.A.; Arya, S.; Koster, C.; Pilgrim, M.G.; Wiatrek-Moumoulidis, D.; van der Spek, P.J.; Hauck, S.M.; Boon, C.J.F.; Emri, E.; Stewart, A.J.; Lengyel, I. On the origin of proteins in human drusen: The meet, greet and stick hypothesis. Prog. Retin. Eye Res., 2019, 70, 55-84.
[http://dx.doi.org/10.1016/j.preteyeres.2018.12.003] [PMID: 30572124]
[7]
Flores-Bellver, M.; Mighty, J.; Aparicio-Domingo, S.; Li, K.V.; Shi, C.; Zhou, J.; Cobb, H.; McGrath, P.; Michelis, G.; Lenhart, P.; Bilousova, G.; Heissel, S.; Rudy, M.J.; Coughlan, C.; Goodspeed, A.E.; Becerra, S.P.; Redenti, S.; Canto-Soler, M.V. Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors. J. Extracell. Vesicles, 2021, 10(13), e12165.
[http://dx.doi.org/10.1002/jev2.12165] [PMID: 34750957]
[8]
Vessey, K.A.; Jobling, A.I.; Tran, M.X.; Wang, A.Y.; Greferath, U.; Fletcher, E.L. Treatments targeting autophagy ameliorate the age-related macular degeneration phenotype in mice lacking APOE (apolipoprotein E). Autophagy, 2022, 18(10), 2368-2384.
[http://dx.doi.org/10.1080/15548627.2022.2034131] [PMID: 35196199]
[9]
Wang, Y.; Fung, N.S.K.; Lam, W.C.; Lo, A.C.Y. mTOR signalling pathway: A potential therapeutic target for ocular neurodegenerative diseases. Antioxidants, 2022, 11(7), 1304.
[http://dx.doi.org/10.3390/antiox11071304] [PMID: 35883796]
[10]
Asatryan, A.; Calandria, J.M.; Kautzmann, M.A.I.; Jun, B.; Gordon, W.C.; Do, K.V.; Bhattacharjee, S.; Pham, T.L.; Bermúdez, V.; Mateos, M.V.; Heap, J.; Bazan, N.G. New retinal pigment epithelial cell model to unravel neuroprotection sensors of neurodegeneration in retinal disease. Front. Neurosci., 2022, 16, 926629.
[http://dx.doi.org/10.3389/fnins.2022.926629] [PMID: 35873810]
[11]
Garcia-Garcia, J.; Usategui-Martin, R.; Sanabria, M.R.; Fernandez-Perez, E.; Telleria, J.J.; Coco-Martin, R.M. Pathophysiology of age-related macular degeneration: Implications for treatment. Ophthalmic Res., 2022, 65(6), 615-636.
[http://dx.doi.org/10.1159/000524942] [PMID: 35613547]
[12]
Mei, L.; Yu, M.; Liu, Y.; Weh, E.; Pawar, M.; Li, L.; Besirli, C.G.; Schwendeman, A.A. Synthetic high-density lipoprotein nanoparticles delivering rapamycin for the treatment of age-related macular degeneration. Nanomedicine, 2022, 44, 102571.
[http://dx.doi.org/10.1016/j.nano.2022.102571] [PMID: 35623563]
[13]
Iachetta, G.; Falanga, A.; Molino, Y.; Masse, M.; Jabès, F.; Mechioukhi, Y.; Laforgia, V.; Khrestchatisky, M.; Galdiero, S.; Valiante, S. gH625-liposomes as tool for pituitary adenylate cyclase-activating polypeptide brain delivery. Sci. Rep., 2019, 9(1), 9183.
[http://dx.doi.org/10.1038/s41598-019-45137-8] [PMID: 31235716]
[14]
Georgiadis, A.; Tschernutter, M.; Bainbridge, J.W.B.; Balaggan, K.S.; Mowat, F.; West, E.L.; Munro, P.M.G.; Thrasher, A.J.; Matter, K.; Balda, M.S.; Ali, R.R. The tight junction associated signalling proteins ZO-1 and ZONAB regulate retinal pigment epithelium homeostasis in mice. PLoS One, 2010, 5(12), e15730.
[http://dx.doi.org/10.1371/journal.pone.0015730] [PMID: 21209887]
[15]
Napoli, D.; Biagioni, M.; Billeri, F.; Di Marco, B.; Orsini, N.; Novelli, E.; Strettoi, E. Retinal pigment epithelium remodeling in mouse models of retinitis pigmentosa. Int. J. Mol. Sci., 2021, 22(10), 5381.
[http://dx.doi.org/10.3390/ijms22105381] [PMID: 34065385]
[16]
Napoli, D.; Strettoi, E. Structural abnormalities of retinal pigment epithelial cells in a light‐inducible, rhodopsin mutant mouse. J. Anat., 2022.
[http://dx.doi.org/10.1111/joa.13667] [PMID: 35428980]
[17]
Pinelli, R.; Bertelli, M.; Scaffidi, E.; Polzella, M.; Fulceri, F.; Biagioni, F.; Fornai, F. Nutraceuticals for dry age-related macular degeneration: A case report based on novel pathogenic and morphological insights. Arch. Ital. Biol., 2020, 158(1), 24-34.
[http://dx.doi.org/10.12871/00039829202013] [PMID: 32575145]
[18]
Chew, E.Y.; Clemons, T.E.; Agrón, E.; Domalpally, A.; Keenan, T.D.L.; Vitale, S.; Weber, C.; Smith, D.C.; Christen, W.; SanGiovanni, J.P.; Ferris, F.L., III; Danis, R.P.; Blodi, B.A.; Ruby, A.J.; Antoszyk, A.; Klein, M.; Kim, I.; Fish, G.E.; Wong, W.T.; Orth, D.H.; Rezaei, K.; Bressler, S.B.; Hubbard, G.B.; Elman, M.J.; Chandra, S.; Friberg, T.; Tolentino, M.; Le, D.; Lansing, M.B.; Stallman, J.B.; Edwards, P.A.; Baker, C.W.; Novak, M.A.; Isernhagen, R.D.; Schneiderman, T.E.; Halperin, L.; Lee, M.; Boyer, D.; Rosenfeld, P.; Rath, P.; Levy, M.; Rosa, R.H., Jr; Hoskins, J.; Chan, C.K.; Brown, D.M.; Greven, C.; Jumper, J.M.; Margulies, L.; Rosenthal, W.; Rosen, R.; Stoller, G.; El Baba, F.; McLean, W.C., Jr; Kingsley, R.; Lyon, A.; Heier, J.; Fung, A.; Scott, I.; Wells, J.; Banach, M.; Beer, P.; Folk, J.; Maguire, J.; Sadda, S.V.; Garfinkel, R.; Kim, J.E.; Berstein, P.; Rauser, M.; Lewis, R.A.; Fishburne, B.C.; Huang, S.; Sabates, N.R.; Kim, N.; Frank, R.N.; Joondeph, B.; Houghton, O.; Hainsworth, D.; Chaum, E.; Millay, R.; Iezzi, R.; Apte, R.; Adelman, R.; Agrawal, A.; Bhagat, N.; Ulanski, L., II; Schwartz, S.; Owsley, C.; Letson, A.J.; He, Y-G.; Toth, C.; Morse, L.; Cooney, M.; Grover, S.; Ferreyra, H.; Brucker, A.J.; DiLoreto, D.; Weinberg, A. Long-term outcomes of adding lutein/zeaxanthin and ω-3 fatty acids to the areds supplements on age-related macular degeneration progression. JAMA Ophthalmol., 2022, 140(7), 692-698.
[http://dx.doi.org/10.1001/jamaophthalmol.2022.1640] [PMID: 35653117]
[19]
Pinelli, R.; Bertelli, M.; Scaffidi, E.; Vakunseth, B.V.; Biagioni, F.; Busceti, C.L.; Puglisi-Allegra, S.; Fornai, F. The neurobiology of nutraceuticals combined with light exposure, a case report in the course of retinal degeneration. Arch. Ital. Biol., 2022, 159(3), 134-150.
[http://dx.doi.org/10.12871/000398292021343] [PMID: 35077571]
[20]
Jin, Q.H.; Hu, X.J.; Zhao, H.Y. Curcumin activates autophagy and attenuates high glucose-induced apoptosis in HUVECs through the ROS/NF-κB signaling pathway. Exp. Ther. Med., 2022, 24(3), 596.
[http://dx.doi.org/10.3892/etm.2022.11533] [PMID: 35949325]
[21]
Munia, I.; Gafray, L.; Bringer, M.A.; Goldschmidt, P.; Proukhnitzky, L.; Jacquemot, N.; Cercy, C.; Ramchani Ben Otman, K.; Errera, M.H.; Ranchon-Cole, I. Cytoprotective effects of natural highly bio-available vegetable derivatives on human-derived retinal cells. Nutrients, 2020, 12(3), 879.
[http://dx.doi.org/10.3390/nu12030879] [PMID: 32214021]
[22]
Vallée, A. Curcumin and Wnt/β-catenin signaling in exudative age-related macular degeneration (Review). Int. J. Mol. Med., 2022, 49(6), 79.
[http://dx.doi.org/10.3892/ijmm.2022.5135] [PMID: 35445729]
[23]
Zhang, Q.; Presswalla, F.; Ali, R.R.; Zacks, D.N.; Thompson, D.A.; Miller, J.M.L. Pharmacologic activation of autophagy without direct mTOR inhibition as a therapeutic strategy for treating dry macular degeneration. Aging, 2021, 13(8), 10866-10890.
[http://dx.doi.org/10.18632/aging.202974] [PMID: 33872219]
[24]
Zhao, X.; Liu, L.; Jiang, Y.; Silva, M.; Zhen, X.; Zheng, W. Protective effect of metformin against hydrogen peroxide-induced oxidative damage in human retinal pigment epithelial (RPE) cells by enhancing autophagy through activation of AMPK pathway. Oxid. Med. Cell. Longev., 2020, 2020, 1-14.
[http://dx.doi.org/10.1155/2020/2524174] [PMID: 32774666]
[25]
Li, S.; Jiang, Y.; Xing, X.; Lin, R.; Li, Q.; Zhou, W.; Qiu, W.; Zheng, W. Protective mechanism of berberine on human retinal pigment epithelial cells against apoptosis induced by hydrogen peroxide via the stimulation of autophagy. Oxid. Med. Cell. Longev., 2021, 2021, 1-14.
[http://dx.doi.org/10.1155/2021/7654143] [PMID: 34422209]
[26]
Hyttinen, J.; Blasiak, J.; Tavi, P.; Kaarniranta, K. Therapeutic potential of PGC-1α in age-related macular degeneration (AMD) – the involvement of mitochondrial quality control, autophagy, and antioxidant response. Expert Opin. Ther. Targets, 2021, 25(9), 773-785.
[http://dx.doi.org/10.1080/14728222.2021.1991913] [PMID: 34637373]
[27]
Hyttinen, J.M.T.; Blasiak, J.; Felszeghy, S.; Kaarniranta, K. MicroRNAs in the regulation of autophagy and their possible use in age-related macular degeneration therapy. Ageing Res. Rev., 2021, 67, 101260.
[http://dx.doi.org/10.1016/j.arr.2021.101260] [PMID: 33516915]
[28]
Blasiak, J.; Pawlowska, E.; Sobczuk, A.; Szczepanska, J.; Kaarniranta, K. The aging stress response and its implication for AMD pathogenesis. Int. J. Mol. Sci., 2020, 21(22), 8840.
[http://dx.doi.org/10.3390/ijms21228840] [PMID: 33266495]
[29]
Paterno, J.J.; Koskela, A.; Hyttinen, J.M.T.; Vattulainen, E.; Synowiec, E.; Tuuminen, R.; Watala, C.; Blasiak, J.; Kaarniranta, K. Autophagy genes for wet age-related macular degeneration in a finnish case-control study. Genes, 2020, 11(11), 1318.
[http://dx.doi.org/10.3390/genes11111318] [PMID: 33172148]

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