AREDS2 sebagai Strategi Perlindungan Retina Terhadap Penuaan: Tinjauan Pustaka dari Perspektif Gerosains
Tinjauan Pustaka
DOI:
https://doi.org/10.55175/cdk.v53i08.2130Kata Kunci:
Age-related macular degeneration, AMD, AREDS2, gerosains, precision geromedicine, geroproteksi retinaAbstrak
Pendahuluan: Degenerasi makula terkait usia (age-related macular degeneration/AMD) merupakan salah satu penyebab utama kehilangan penglihatan permanen pada populasi lanjut usia. Suplementasi Age-Related Eye Disease Study 2 (AREDS2) dikembangkan sebagai strategi nutraseutikal berbasis bukti untuk memperlambat progresivitas AMD. Artikel ini menelaah bukti klinis serta potensi penerapan AREDS2 sebagai intervensi geroprotektif pada retina dalam kerangka precision geromedicine. Metode: Tinjauan naratif terhadap berbagai penelitian terbaru mengenai AREDS dan AREDS2 dilakukan dengan mengintegrasikan konsep-konsep gerosains yang berkaitan dengan proses penuaan retina. Hasil: Formulasi AREDS2, yang menggantikan beta-carotene dengan lutein dan zeaxanthin, terbukti menurunkan risiko progresivitas AMD sebesar 18% tanpa meningkatkan risiko kanker paru pada perokok. Komponen AREDS2 menargetkan berbagai jalur utama yang berperan dalam proses penuaan, termasuk stres oksidatif, disfungsi mitokondria, inflamasi kronis, serta disregulasi autofagi. Selain itu, potensi modulasi jalur pensinyalan mTOR dan AMPK menunjukkan bahwa AREDS2 dapat berperan dalam memperpanjang healthspan retina. Simpulan: AREDS2 merupakan pendekatan nutraseutikal yang menjanjikan sebagai terapi geroprotektif retina dalam paradigma precision geromedicine. Implikasi klinisnya meliputi pencegahan progresivitas AMD, optimalisasi fungsi penglihatan pada populasi lanjut usia, serta peluang integrasi ke dalam praktik oftalmologi berbasis presisi. Penelitian lebih lanjut masih diperlukan untuk memvalidasi mekanisme molekuler yang mendasarinya serta mengevaluasi efektivitasnya pada berbagai populasi, sehingga dapat memperkuat peran AREDS2 dalam intervensi kesehatan mata terkait penuaan secara lebih luas.
Unduhan
Referensi
Kashi AK, Souied E, Fares S, Borrelli E, Capuano V, Jung C, et al. The spectrum of central choriocapillaris abnormalities on swept-source optical coherence tomography angiography in the fellow eye of unilateral exudative age-related macular degeneration patients: from flow deficits to subclinical non-exudative neovascularization. J Clin Med. 2021;10(12):2658. doi: 10.3390/JCM10122658.
Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J. Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments. Arch Ophthalmol. 2009;127(4):533–40. doi: 10.1001/ARCHOPHTHALMOL.2009.58.
Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye and vision (London, England) 2016;3:34. https://doi.org/10.1186/s40662-016-0063-5.
Vyawahare H, Shinde,P. Age-related macular degeneration: epidemiology, pathophysiology, diagnosis, and treatment. Cureus 2022;14(9):e29583. https://doi.org/10.7759/cureus.29583.
Guo J, Huang X, Dou L, Yan M, Shen T, Tang W, et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduction Targeted Ther. 2022;7(1):1–40. https://doi.org/10.1038/s41392-022-01251-0.
Iakovou E, Kourti M. A comprehensive overview of the complex role of oxidative stress in aging, the contributing environmental stressors and emerging antioxidant therapeutic interventions. Front Aging Neurosci. 2022;14:827900. https://doi.org/10.3389/fnagi.2022.827900.
Upadhyay M, Bonilha V. Analysis of oxidative stress-mediated degeneration in retina and RPE using sodium iodate (NaIO3) model. Free Radic Biol Med. 2018;128:S128. doi: 10.1016/J.FREERADBIOMED.2018.10.318.
Prea SM Chan, EC, Dusting GJ, Vingrys AJ, Bui BV, Liu GS, et al. Gene therapy with endogenous inhibitors of angiogenesis for neovascular age-related macular degeneration: beyond anti-VEGF therapy. J Ophthalmol. 2015;1:201726. https://doi.org/10.1155/2015/201726.
Langford-Smith A, Keenan TDL, Clark SJ, Bishop PN, Day AJ. The role of complement in age-related macular degeneration: Heparan sulphate,a ZIP code for complement factor H?. J Innate Immun. 2014;6(4):407–16. doi: 10.1159/000356513.
Suzumura A, Terao R, Kaneko H. Protective effects and molecular signaling of n-3 fatty acids on oxidative stress and inflammation in retinal diseases. Antioxidants. 2020;9(10):920. doi: 10.3390/ANTIOX9100920.
Awh CC, Lane AM, Hawken S, Zanke B, Kim IK. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology. 2013;120(11):2317–23. doi: 10.1016/J.OPHTHA.2013.07.039.
Wang L, Chen Y, Sternberg P, Cai J. Essential roles of the PI3 kinase/akt pathway in regulating Nrf2-dependent antioxidant functions in the RPE. Invest Ophthalmol Vis Sci. 2008;49(4):1671–8. doi: 10.1167/IOVS.07-1099.
Wang D, Chen Y, Li J, Wu E, Tang T, Singla RK, et al. Natural products for the treatment of age-related macular degeneration. Phytomedicine. 2024;130:155522. https://doi.org/10.1016/j.phymed.2024.155522.
Iakovou E, Kourti M. A comprehensive overview of the complex role of oxidative stress in aging, the contributing environmental stressors and emerging antioxidant therapeutic interventions. Front Aging Neurosc. 2022;14:827900. https://doi.org/10.3389/fnagi.2022.827900.
Reinisalo M, Karlund A, Koskela A, Kaarniranta K, Karjalainen RO. Polyphenol stilbenes: molecular mechanisms of defence against oxidative stress and aging-related diseases. Oxidative Med Cell Longevity. 2015;2015:340520. https://doi.org/10.1155/2015/340520.
Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients 2017;9(12):1286. https://doi.org/10.3390/nu9121286.
Basyal D, Lee S, Kim HJ. Antioxidants and mechanistic insights for managing dry age-related macular degeneration. Antioxidants (Basel). 2024;13(5):568. https://doi.org/10.3390/antiox13050568.
Marino N, Putignano G, Cappilli S, Chersoni E, Santuccione A, Calabrese G, et al. Towards AI-driven longevity research: a overview. Front Aging. 2023;4:1057204. https://doi.org/10.3389/fragi.2023.1057204.
Shanaida M, Mykhailenko O, Lysiuk R, Hudz N, Balwierz R, Shulhai A, et al. Carotenoids for antiaging: nutraceutical, pharmaceutical, and cosmeceutical applications. Pharmaceuticals 2025;18(3):403. https://doi.org/10.3390/ph18030403.
Parmar UPS, Surico PL, Mori T, Singh RB, Cutrupi F, Premkishore P, et al. Antioxidants in age-related macular degeneration: lights and shadows. Antioxidants (Basel). 2025;14(2):152. https://doi.org/10.3390/antiox14020152.
Alugoju P, Krishna Swamy VKD, Anthikapalli NVA, Tencomnao T. Health benefits of astaxanthin against age-related diseases of multiple organs: a comprehensive review. Crit Rev Food Sci Nutr. 2023;63(31):10709–74. doi:10.1080/10408398.2022.2084600.
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243–78. doi:10.1016/J.CELL.2022.11.001.
Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, et al. Geroscience: linking aging to chronic disease. Cell. 2014;159(4):709–13. doi: 10.1016/J.CELL.2014.10.039.
Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. From discoveries in ageing research to therapeutics for healthy ageing. Nature. 2019;571(7764):183–92. doi: 10.1038/S41586-019-1365-2.
Sivaprasad S, Chong N V. The complement system and age-related macular degeneration. Eye. 2006;20(8):867–72. doi: 10.1038/SJ.EYE.6702176.
Wong KH, Nam HY, Lew SY, Naidu M, David P, Kamalden TA, et al. Discovering the potential of natural antioxidants in age-related macular degeneration: a review. Pharmaceuticals (Basel). 2022 Jan 14;15(1):101. doi: 10.3390/ph15010101.
Buonfiglio F, Korb CA, Stoffelns B, Pfeiffer N, Gericke A. Recent advances in our understanding of age-related macular degeneration: mitochondrial dysfunction, redox signaling, and the complement system. Aging Dis. 2024;16(3):1535–75. doi: 10.14336/AD.2024.0124.
Chew EY, Clemons T, SanGiovanni JP, Danis R, Domalpally A, McBee W, et al. The Age-Related Eye Disease Study 2 (AREDS2): study design and baseline characteristics (AREDS2 report no 1). Ophthalmology. 2012;119(11):2282–9. doi: 10.1016/J.OPHTHA.2012.05.027.
Suzumura A, Terao R, Kaneko H. Protective effects and molecular signaling of n-3 fatty acids on oxidative stress and inflammation in retinal diseases. Antioxidants (Basel). 2020;9(10):920. doi: 10.3390/ANTIOX9100920.
Mrowicka M, Mrowicki J, Kucharska,E, Majsterek I. Lutein and zeaxanthin and their roles in age-related macular degeneration-neurodegenerative disease. Nutrients 2022;14(4):827. https://doi.org/10.3390/nu14040827.
Wong KH, Nam HY, Lew SY, Naidu M, David P, Kamalden TA, et al. Discovering the potential of natural antioxidants in age-related macular degeneration: a review. Pharmaceuticals (Basel, Switzerland) 2022;15(1):01. https://doi.org/10.3390/ph15010101.
Fingar DC, Blenis J. Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene. 2004;23(18):3151–71. doi:10.1038/SJ.ONC.1207542.
Lambert NG, ElShelmani H, Singh MK, Mansergh FC, Wride MA, Padilla M, et al. Risk factors and biomarkers of age-related macular degeneration. Prog Retin Eye Res. 2016;54:64–102. doi: 10.1016/J.PRETEYERES.2016.04.003.
Bian Q, Gao S, Zhou J, Qin J, Taylor A, Johnson EJ, et al. Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells. Free Radic Biol Med. 2012;53(6):1298–307. doi:10.1016/J.FREERADBIOMED.2012.06.024.
Tuo J, Ross RJ, Herzlich AA, Shen D, Ding X, Zhou M, et al. A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration. Am J Pathol. 2009;175(2):799–807. doi: 10.2353/AJPATH.2009.090089.
Detaram DH, Mitchell P, Russell J, Burlutsky G, Liew G, Gopinath B. Dietary zinc intake is associated with macular fluid in neovascular agerelated macular degeneration. Clin Exp Ophthalmol. 2020;48(1):61–8. doi: 10.1111/CEO.13644.
Gemenetzi M, Lotery AJ. Complement pathway biomarkers and age-related macular degeneration. Eye (Lond). 2016;30(1):1–14. doi:10.1038/EYE.2015.203.
Unduhan
Diterbitkan
Cara Mengutip
Terbitan
Bagian
Lisensi
Hak Cipta (c) 2026 Bhirau Wilaksono, Enno Elfandari, Rayhani Ichsan, A. Dhini Alfiandari, Nurul Muf'idah Damry, Andi Makkawaru Chairul, Nurul Mutiah Aminuddin, Novi Safitri Nurdin, Aida Ayu Chandrawati, Nurussyariah Hammado
Artikel ini berlisensi Creative Commons Attribution-NonCommercial 4.0 International License.
