Cerium oxide nanoparticles mitigate retinal pigment epithelium (RPE) death using APRE19 cell model

Document Type : Research Paper


1 New York Institute of Technology College of Medicine, Old Westbury, NY, USA

2 Massachusetts Eye & Ear Infirmary, Boston, MA, USA

3 Department of Chemical Engineering, Northeastern University, Boston, MA, USA


Objective(s): In this study, we present the potential of cerium oxide nanoparticle pretreatment on ARPE-19 cells, a cell line of the Retinal Pigment Epithelium (RPE), as a therapeutic modality to cellular stresses such as low serum starvation.
Materials and Methods: ARPE-19 cells were pretreated with nano-cerium oxide at a concentration of 500 µg/mL before low serum stress was induced for 24, 48, 72, and 96 hours. Starvation stress was induced by using low concentrations of Fetal Bovine Serum (FBS) media at three increments: 10%, 1%, 0.1%.
Results: Contrast images demonstrated higher cell confluence and cell integrity in cells pretreated with cerium oxide nanoparticles compared to untreated cells. Increased cell viability for cerium oxide pretreated cells was confirmed by MTS assay after 96 hours of serum starvation.
Conclusion: By using nanoparticles to influence pathways of apoptosis, we hope to rescue ARPE-19 cells from a range of stressors, including oxidative stress, and re-establish homeostasis for the cell. Nanoparticles may represent a novel class of therapeutics for diseases of the eye, like AMD and blue-light induced oxidative stress.


1.Knickelbein JE, Chan CC, Sen HN, Ferris FL, Nussenblatt RB. Inflammatory Mechanisms of Age-related Macular Degeneration. Int Ophthalmol Clin. 2015; 55(3): 63-78.
2.Datta S, Cano M, Ebrahimi K, Wang L, Handa JT. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res. 2017; 60:201-218.
3.Nita M, Strzałka-Mrozik B, Grzybowski A, Mazurek U, Romaniuk W. Age-related macular degeneration and changes in the extracellular matrix. Med Sci Monit. 2014; 20:1003- 1016.
4.Blasiak J, Piechota M, Pawlowska E, Szatkowska M, Sikora E, Kaarniranta K. Cellular Senescence in Age-Related Macular Degeneration: Can Autophagy and DNA Damage Response Play a Role?. Oxid Med Cell Longev. 2017; 2017: 5293258.
5.Bellezza I. Oxidative Stress in Age-Related Macular Degeneration: Nrf2 as Therapeutic Target. Front Pharmacol. 2018; 9: 1280.
6.Rohowetz LJ, Kraus JG, Koulen P. Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina. Int J Mol Sci. 2018; 19(11): 3362.
7.Kunchithapautham K, Atkinson C, Rohrer B. Smoke exposure causes endoplasmic reticulum stress and lipid accumulation in retinal pigment epithelium through oxidative stress and complement activation. J Biol Chem. 2014; 289(21): 14534-14546.
8.Al-Zamil WM, Yassin SA. Recent developments in age-related macular degeneration: a review. Clin Interv Aging. 2017; 12: 1313-1330.
9.Kaliappan S, Jha P, Lyzogubov VV, Tytarenko RG, Bora NS, Bora PS. Alcohol and nicotine consumption exacerbates choroidal neovascularization by modulating the regulation of complement system. FEBS Lett. 2008; 582(23-24): 3451-3458.
10.Heesterbeek TJ, Lorés-Motta L, Hoyng CB, Lechanteur YTE, den Hollander AI. Risk factors for progression of age-related macular degeneration. Ophthalmic Physiol Opt. 2020; 40(2): 140-170.
11.Abokyi S, To CH, Lam TT, Tse DY. Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models. Oxid Med Cell Longev. 2020; 2020: 7901270.
12.Galor A, Feuer W, Kempen JH, et al. Adverse effects of smoking on patients with ocular inflammation. Br J Ophthalmol. 2010; 94(7): 848-853.
13.Murat Dogru, Takashi Kojima, Cem Simsek, Kazuo Tsubota; Potential Role of Oxidative Stress in Ocular Surface Inflammation and Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2018; 59(14): 163-168.
14.Golabchi K, Abtahi MA, Salehi A, Jahanbani-Ardakani H, Ghaffari S, Farajzadegan Z. The effects of smoking on corneal endothelial cells: a cross-sectional study on a population from Isfahan, Iran. Cutan Ocul Toxicol. 2018; 37(1): 9-14.
15.Kim GH, Kim HI, Paik SS, Jung SW, Kang S, Kim IB. Functional and morphological evaluation of blue light-emitting diode-induced retinal degeneration in mice. Graefes Arch Clin Exp Ophthalmol. 2016; 254(4): 705-716.
16.Zinflou C, Rochette PJ. Absorption of blue light by cigarette smoke components is highly toxic for retinal pigmented epithelial cells. Arch Toxicol. 2019; 93(2): 453-465.
17.Tosini G, Ferguson I, Tsubota K. Effects of blue light on the circadian system and eye physiology. Mol Vis. 2016; 22: 61-72.
18.Moon J, Yun J, Yoon YD, et al. Blue light effect on retinal pigment epithelial cells by display devices. Integr Biol (Camb). 2017; 9(5): 436-443.
19.Dunn KC, Aotaki-Keen AE, Putkey FR, Hjelmeland LM. ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp Eye Res. 1996; 62(2): 155-169.
20.Yuan B, Webster TJ, Roy AK. Cytoprotective effects of cerium and selenium nanoparticles on heat-shocked human dermal fibroblasts: an in vitro evaluation. Int J Nanomedicine. 2016; 11: 1427-1433.
21.Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019; 20(3): 175-193.