Skip to main content Accessibility help

Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells

  • Yixiang Liu (a1), Xue Song (a1), Di Zhang (a1), Feng Zhou (a1), Dan Wang (a1), Ying Wei (a1), Fengyi Gao (a1), Liyang Xie (a1), Gang Jia (a1), Wei Wu (a2) and Baoping Ji (a1)...


Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100–380 nm) and visible (380–760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (sd 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (sd 500) lx light (420–800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells
      Available formats


Corresponding author

*Corresponding author: Professor B. Ji, fax +86 10 62347334, email


Hide All
1Sparrrow, JR, Hicks, D & Hamel, CP (2010) The retinal pigment epithelium in health and disease. Curr Mol Med 10, 802823.
2McBlee, JK, Palczewski, K, Baehr, W, et al. (2001) Confronting complexity: the interlink of phototransduction and retinoid metabolism in the vertebrate retina. Prog Retin Eye Res 20, 469529.
3Qin, S & Rodrigues, GA (2008) Progress and perspectives on the role of RPE cell inflammatory responses in the development of age-related macular degeneration. Inflamm Res 1, 4965.
4Zhu, DH, Deng, X, Xu, J, et al. (2008) What determines the switch between atrophic and neovascular forms of age related macular degeneration? The role of BMP4 induced senescence. Ageing 1, 740745.
5Rattner, A, Toulabi, L, Williams, J, et al. (2008) The genomic response of the retinal pigment epithelium to light damage and retinal detachment. J Neurosci 28, 98809889.
6Herbig, U, Ferreira, M, Condel, L, et al. (2006) Cellular senescence in aging primates. Science 311, 1257.
7Pendergrass, WR, Lane, MA, Bodkin, NL, et al. (1999) Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta). J Cell Physiol 180, 123130.
8Ressler, S, Bartkova, J, Niederegger, H, et al. (2006) P16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell 5, 379389.
9Foreman, KE & Tang, J (2003) Molecular mechanisms of replicative senescence in endothelial cells. Exp Gerontol 38, 12511257.
10Li, Y, Wang, YS, Shen, XF, et al. (2008) Alterations of activity and intracellular distribution of the 20S proteasome in ageing retinal pigment epithelial cells. Exp Gerontol 43, 11141122.
11Toussaint, O, Medrano, EE & Von Zglinicki, T (2000) Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp Gerontol 35, 927945.
12Roider, J, Brinkmann, R, Wirbelauer, C, et al. (1999) Variability of RPE reaction in two cases after selective RPE laser effects in prophylactic treatment of drusen. Graefes Arch Clin Exp Ophthalmol 237, 4550.
13Rastmanesh, R (2011) Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity. Med Hypotheses 76, 7985.
14Boulton, M, Róanowska, M & Wess, T (2004) Ageing of the retinal pigment epithelium: implications for transplantation. Graefes Arch Clin Exp Ophthalmol 242, 7684.
15Zarbin, MA (2004) Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 122, 598614.
16Chen, H, Liu, B, Lukas, TJ, et al. (2008) The aged retinal pigment epithelium/choroid: a potential substratum for the pathogenesis of age-related macular degeneration. PLoS ONE 3, e2339.
17Algvere, PV, Marshall, J & Seregard, S (2006) Age-related maculopathy and the impact of light hazard. Acta Ophthalmol Scand 84, 415.
18Youn, HY, Chou, BR, Cullen, AP, et al. (2009) Effects of 400 nm, 420 nm, and 435·8 nm radiations on cultured human retinal pigment epithelial cells. J Photochem Photobiol B 95, 6470.
19Shiraga, S, Adamus, G, Shiraga, S, et al. (2002) Mechanism of CAR syndrome: anti-recoverin antibodies are the inducers of retinal cell apoptotic death via the caspase 9-and caspase 3-dependent pathway. J Neuroimmunol 132, 7282.
20Skilling, FC, Weaver, TA, Kato, KP, et al. (2005) Effects of two eye drop products on computer users with subjective ocular discomfort. Optometry 76, 4754.
21Boulton, M, Rozanowska, M & Rozanowski, B (2001) Retinal photodamage. J Photochem Photobiol B 64, 144161.
22Wenzel, A, Grimm, C, Samardzija, M, et al. (2005) Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res 24, 275306.
23Roehlecke, C, Schaller, A, Knels, L, et al. (2009) The influence of sublethal blue light exposure on human RPE cells. Mol Vis 15, 19291938.
24Sparrow, JR, Vollmer-Snarr, HR, Zhou, JL, et al. (2003) A2E-epoxides damage DNA in retinal pigment epithelial cells. J Biol Chem 278, 1820718213.
25King, A, Gottlieb, E, Brooks, DG, et al. (2004) Mitochondria-derived reactive oxygen species mediate blue light-induced death of retinal pigment epithelial cells. Photochem Photobiol 79, 470475.
26Rezai, KA, Gasyna, E, Seagle, BL, et al. (2008) AcrySof Natural filter decreases blue light-induced apoptosis in human retinal pigment epithelium. Graefes Arch Clin Exp Ophthalmol 246, 671676.
27Zheng, Y, Liang, H, Hao, C, et al. (2008) Computer vision syndrome: a widely spreading but largely unknown epidemic among computer users. Comput Human Behav 24, 20262042.
28Tanito, M, Kwon, YW, Kondo, N, et al. (2005) Cytoprotective effects of geranyl-geranylacetone against retinal photooxidative damage. J Neurosci 25, 23962404.
29Xie, ZG, Wu, XW, Gong, YY, et al. (2007) Intraperitoneal injection of Ginkgo biloba extract enhances antioxidation ability of retina and protects photoreceptors after light-induced retinal damage in rats. Curr Eye Res 32, 471479.
30Chen, L, Wu, W, Dentchev, T, et al. (2004) Increased metallothionein in light damaged mouse retinas. Exp Eye Res 79, 287293.
31Kalt, W, Hanneken, A, Milbury, P, et al. (2010) Recent research on polyphenolics in vision and eye health. J Agric Food Chem 58, 40014007.
32Jang, YP, Zhou, J, Nakanishi, K, et al. (2005) Anthocyanins protect against A2E photooxidation and membrane permeabilization in retinal pigment epithelial cells. Photochem Photobiol 81, 529536.
33Matsumoto, H, Nakamura, Y, Iido, H, et al. (2006) Comparative assessment of distribution of blackcurrant anthocyanins in rabbit and rat ocular tissues. Exp Eye Res 83, 348356.
34Kalt, W, Berg, JB, Mcdonald, JE, et al. (2008) Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs. J Agric Food Chem 56, 705712.
35Kim, DO, Heo, HJ, Kim, YJ, et al. (2005) Sweet and sour cherry phenolics and their protective effects on neuronal cells. J Agric Food Chem 53, 99219927.
36Yi, W, Fischer, J, Krewer, G, et al. (2005) Phenolic compounds from blueberries can inhibit colon cancer cell proliferation and induce apoptosis. J Agric Food Chem 53, 73207329.
37Singleton, VL & Rossi, JA (1965) Colorimetry of total phenolics with phosphor-molybdic-phosphotungstic acid reagent. Am J Enol Viticult 16, 144158.
38You, Q, Wang, B, Chen, F, et al. (2011) Comparison of anthocyanins and phenolics in organically and conventionally grown blueberries in selected cultivars. Food Chem 125, 201208.
39Giusti, MM & Wrolstad, RE (2001) Anthocyanins characterization and measurement with UV-visible spectroscopy. In Current Protocols in Food Analytical Chemistry, Unit F1·2, pp. 113 [Wrolstad, RE, editor]. New York, NY: Wiley Press.
40Hui, S, Yi, L & Fengling, QL (2009) Effects of light exposure and use of intraocular lens on retinal pigment epithelial cells in vitro. Photochem Photobiol 85, 966969.
41Zhang, W & Popovich, DG (2008) Effect of soyasapogenol A and soyasapogenol B concentrated extracts on HepG-2 cell proliferation and apoptosis. J Agric Food Chem 56, 26032608.
42Wilhelm, J, Vytasek, R, Ostadalova, I, et al. (2009) Evaluation of different methods detecting intracellular generation of free radicals. Mol Cell Biochem 328, 167176.
43Lee, J & Finn, CE (2007) Anthocyanins and other polyphenolics in American elderberry (Sambucus canadensis) and European elderberry (S. nigra) cultivars. J Sci Food Agric 87, 26652675.
44Lee, J, Rennaker, C & Wrolstad, RE (2008) Correlation of two anthocyanin quantification methods: HPLC and spectrophotometric methods. Food Chem 110, 782786.
45Feher, J, Kovacs, I, Artico, M, et al. (2006) Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Aging 27, 983993.
46Jeyapalan, JC & Sedivy, JM (2008) Cellular senescence and organismal aging. Mech Ageing Dev 129, 467474.
47Bree, RT, Stenson-Cox, C, Grealy, M, et al. (2002) Cellular longevity: role of apoptosis and replicative senescence. Biogerontology 3, 195206.
48Seluanov, A, Gorbunova, V, Falcovitz, A, et al. (2001) Change of the death pathway in senescent human fibrolasts in response to DNA damage is caused by an inability to stabilize p53. Mol Cell Biol 21, 15521564.
49Passos, JF & Zglinicki, T (2005) Mitochondria, telomeres and cell senescence. Exp Gerontol 40, 466472.
50Chen, Y, Wang, J, Cai, J, et al. (2010) Altered mTOR signaling in senescent retinal pigment epithelium. Invest Ophth Vis Sci 51, 53145319.
51Li, W, Yanoff, M, Li, Y, et al. (1999) Artificial senescence of bovine retinal pigment epithelial cells induced by near-ultraviolet in vitro. Mech Ageing Dev 110, 137155.
52Honda, S, Hjelmeland, LM & Handa, JT (2002) Senescence associated beta-galactosidase activity in human retinal pigment epithelial cells exposed to mild hyperoxia in vitro. Br J Ophthalmol 86, 159162.
53Yu, AL, Fuchahofer, R, Kook, D, et al. (2009) Subtoxic oxidative stress induces senescence in retinal pigment epithelial cells via TGF-α release. Invest Ophth Vis Sci 50, 926935.
54Kook, D, Wolf, AH, Yu, AL, et al. (2009) Accumulation of large protein fragments in prematurely senescent ARPE-19 cells. Invest Ophth Vis Sci 50, 49924997.
55Yu, AL, Lorenz, RL, Haritoglou, C, et al. (2009) Biological effects of native and oxidized low-density lipoproteins in cultured human retinal pigment epithelial cells. Exp Eye Res 88, 495503.
56Welge-Lussen, UC (2008) The protective effect of quercetin against oxidative stress in the human RPE in vitro. Invest Ophth Vis Sci 49, 17121720.
57Sparrow, JR & Cai, B (2001) Blue light-induced apoptosis of A2E containing RPE: involvement of caspase-3 and protection by Bcl-2. Invest Ophthalmol Vis Sci 42, 13561362.
58Portt, L, Norman, G, Clapp, C, et al. (2011) Anti-apoptosis and cell survival: a review. Biochim Biophys Acta 1813, 238259.
59Milbury, PE, Graf, BA, Berg, JB, et al. (2005) Anthocyanins cross the blood–brain barrier: effects on oxidative stress-induced apoptosis. 229th ACS National Meeting, 1317. San Diego, CA.
60Penumathsa, SV, Koneru, S, Samuel, SM, et al. (2008) Strategic targets to induce neovascularization by resveratrol in hypercholesterolemic rat myocardium: role of caveolin-1, endothelial nitric oxide synthase, hemeoxygenase-1, and vascular endothelial growth factor. Free Radic Bio Med 45, 10271034.
61Mennel, S, Peter, S, Meyer, CH, et al. (2006) Effect of photodynamic therapy on the function of the outer blood–retinal barrier in an in vitro model. Graefe's Arch Clin Exp Ophthalmol 244, 10151021.
62Hurst, RD, Wells, RW, Hurst, SM, et al. (2010) Blueberry fruit polyphenolics suppress oxidative stress induced skeletal muscle cell damage in vitro. Mol Nutr Food Res 54, 353363.
63Liu, Y, Song, X, Han, Y, et al. (2011) Identification of anthocyanin components of wild Chinese blueberries and amelioration of light-induced retinal damage in pigmented rabbit using whole berries. J Agric Food Chem 59, 356363.
64Kay, CD, Mazza, G, Holub, BJ, et al. (2004) Anthocyanin metabolites in human serum and urine. Br J Nutr 91, 933942.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed