Effect of a Complex Lutein Formula in an Animal Model for Light-Induced Retinal Degeneration

10.4077/CJP.2016.BAE404

Yin-Pin Cheng；Chia-Ying Ke；Chih-Chieh Kuo；Yih-Jing Lee

electroretinogram ； light expose ； lutein ； photoreceptor ； retinal degeneration

The Chinese Journal of Physiology

59卷4期（2016 / 08 / 31）

202 - 209

英文

Several retinal degenerative diseases cause vision loss and retinal cell death. Currently, people face prolonged exposure to digital screens, rendering vision protection from light exposure a critical topic. In this study, we designed a complex lutein formula (CLF) by combining several natural compounds: Calendula officinalis, Lycium barbarum, Vaccinium myrtillus, Cassia obtusifolia, and Rhodiola rosea. In addition, we evaluated the protective effects of the formula on retinal functions in an animal model for light-induced retinal degeneration. We employed electroretinography to analyse retinal function, and conducted a histological examination of the morphological changes in the retina treated under various conditions. We revealed that the retinal function in animals exposed to light for 7 days decreased significantly; however, the retinal function of animals that had received the CLF exhibited superior performance, despite light exposure. In addition, a greater portion of the outer nuclear layer (ONL) (i.e. the nuclei of photoreceptors) in these animals was preserved compared with the animals that had not received the formula after 7 days of light exposure. These results revealed that our dietary CLF supplement attenuated retinal function loss resulting from long-term light exposure.

1. Liu, H.,Sun, H.,Liu, C.(2011).Interference of the apoptotic signaling pathway in RGC stress response by SP600125 in moderate ocular hypertensive rats.Chinese J. Physiol.,54,124-132.
   連結：
2. Ahmad, H.,Khan, I.,Wahid, A.(2012).Antiglycation and antioxidation properties of Juglans regia and Calendula officinalis: possible role in reducing diabetic complications and slowing down ageing.J. Tradit. Chinese Med.,32,411-414.
3. Bako, E.,Deli, J.,Toth, G.(2002).HPLC study on the carotenoid composition of Calendula products.J. Biochem. Biophys. Methods,53,241-250.
4. Bawa, A.S.,Khanum, F.(2009).Anti-inflammatory activity of Rhodiola rosea-"a second-generation adaptogen".Phytother. Res.,23,1099-1102.
5. Bian, Q.,Gao, S.,Zhou, J.,Qin, J.,Taylor, A.,Johnson, E.J.,Tang, G.,Sparrow, J.R.,Gierhart, D.,Shang, F.(2012).Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells.Free Radic. Biol. Med.,53,1298-1307.
6. Bok, D.,Yasumura, D.,Matthes, M.T.,Ruiz, A.,Duncan, J.L.,Chappelow, A.V.,Zolutukhin, S.,Hauswirth, W.,LaVail, M.M.(2002).Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation.Exp. Eye Res.,74,719-735.
7. Bone, R.A.,Landrum, J.T.,Friedes, L.M.,Gomez, C.M.,Kilburn, M.D.,Menendez, E.,Vidal, I.,Wang, W.(1997).Distribution of lutein and zeaxanthin stereoisomers in the human retina.Exp. Eye Res.,64,211-218.
8. Bone, R.A.,Landrum, J.T.,Guerra, L.H.,Ruiz, C.A.(2003).Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans.J. Nutr.,133,992-998.
9. Canter, P.H.,Ernst, E.(2004).Anthocyanosides of Vaccinium myrtillus (bilberry) for night vision-a systematic review of placebocontrolled trials.Surv. Ophthalmol.,49,38-50.
10. Chandran, P.K.,Kuttan, R.(2008).Effect of Calendula officinalis flower extract on acute phase proteins, antioxidant defense mechanism and granuloma formation during thermal burns.J. Clin. Biochem. Nutr,43,58-64.
11. Cho, S.H.,Kim, T.H.,Lee, N.H.,Son, H.S.,Cho, I.J.,Ha, T.Y.(2005).Effects of Cassia tora fiber supplement on serum lipids in Korean diabetic patients.J. Med. Food,8,311-318.
12. Della Loggia, R.,Tubaro, A.,Sosa, S.,Becker, H.,Saar, S.,Isaac, O.(1994).The role of triterpenoids in the topical anti-inflammatory activity of Calendula officinalis flowers.Planta Med.,60,516-520.
13. Faria, A.,Oliveira, J.,Neves, P.,Gameiro, P.,Santos-Buelga, C.,de Freitas, V.,Mateus, N.(2005).Antioxidant properties of prepared blueberry (Vaccinium myrtillus) extracts.J. Agric. Food Chem.,53,6896-6902.
14. Fonseca, Y.M.,Catini, C.D.,Vicentini, F.T.,Nomizo, A.,Gerlach, R.F.,Fonseca, M.J.(2010).Protective effect of Calendula officinalis extract against UVB-induced oxidative stress in skin: evaluation of reduced glutathione levels and matrix metalloproteinase secretion.J. Ethnopharmacol.,127,596-601.
15. Ganzera, M.,Yayla, Y.,Khan, I.A.(2001).Analysis of the marker compounds of Rhodiola rosea L. (golden root) by reversed phase high performance liquid chromatography.Chem. Pharm. Bull.,49,465-467.
16. Gordon, W.C.,Casey, D.M.,Lukiw, W.J.,Bazan, N.G.(2002).DNA damage and repair in light-induced photoreceptor degeneration.Invest. Ophthalmol. Vis. Sci.,43,3511-3521.
17. Grimm, C.,Wenzel, A.,Hafezi, F.,Yu, S.,Redmond, T.,Rem, C.(2000).Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration.Nat. Genet.,25,63-66.
18. Handelman, G.J.,Dratz, E.A.,Reay, C.C.,van Kuijk, J.G.(1988).Carotenoids in the human macula and whole retina.Invest. Ophthalmol. Vis. Sci.,29,850-855.
19. Hao, W.,Wenzel, A.,Obin, M.S.,Chen, C.K.,Brill, E.,Krasnoperova, N.V.,Eversole-Cire, P.,Kleyner, Y.,Taylor, A.,Simon, M.I.,Grimm, C.,Reme, C.E.,Lem, J.(2002).Evidence for two apoptotic pathways in light-induced retinal degeneration.Nat. Genet.,32,254-260.
20. Hollyfield, J.G.,Bonilha, V.L.,Rayborn, M.E.,Yang, X.,Shadrach, K.G.,Lu, L.,Ufret, R.L.,Salomon, R.G.,Perez, V.L.(2008).Oxidative damage-induced inflammation initiates age-related macular degeneration.Nat. Med.,14,194-198.
21. Hu, C.K.,Lee, Y.J.,Colitz, C.M.,Chang, C.J.,Lin, C.T.(2012).The protective effects of Lycium barbarum and Chrysanthemum morifolum on diabetic retinopathies in rats.Vet. Ophthalmol.,15(Suppl 2),65-71.
22. Joly, S.,Pernet, V.,Dorfman, A.L.,Chemtob, S.,Lachapelle, P.(2006).Light-induced retinopathy: comparing adult and juvenile rats.Invest. Ophthalmol. Vis. Sci.,47,3202-3212.
23. Ju, M.S.,Kim, H.G.,Choi, J.G.,Ryu, J.H.,Hur, J.,Kim, Y.J.,Oh, M.S.(2010).Cassiae semen, a seed of Cassia obtusifolia, has neuroprotective effects in Parkinson's disease models.Food Chem. Toxicol.,48,2037-2044.
24. Kim, D.H.,Kim, S.,Jung, W.Y.,Park, S.J.,Park, D.H.,Kim, J.M.,Cheong, J.H.,Ryu, J.H.(2009).The neuroprotective effects of the seeds of Cassia obtusifolia on transient cerebral global ischemia in mice.Food Chem. Toxicol.,47,1473-1479.
25. Kishimoto, S.,Maoka, T.,Sumitomo, K.,Ohmiya, A.(2005).Analysis of carotenoid composition in petals of calendula (Calendula officinalis L.).Biosci. Biotechnol. Biochem.,69,2122-2128.
26. Kitanaka, S.,Nakayama, T.,Shibano, T.,Ohkoshi, E.,Takido, M.(1998).Antiallergic agent from natural sources. Structures and inhibitory effect of histamine release of naphthopyrone glycosides from seeds of Cassia obtusifolia L.Chem. Pharm. Bull.,46,1650-1652.
27. Kitanaka, S.,Takido, M.(1986).Studies on the constituents in the roots of Cassia obtusifolia L. and the antimicrobial activities of constituents of the roots and the seeds.Yakugaku Zasshi,106,302-306.
28. Kvansakul, J.,Rodriguez-Carmona, M.,Edgar, D.F.,Barker, F.M.,Kopcke, W.,Schalch, W.,Barbur, J.L.(2006).Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance.Ophthalmic. Physiol. Opt.,26,362-371.
29. Latti, A.K.,Riihinen, K.R.,Kainulainen, P.S.(2008).Analysis of anthocyanin variation in wild populations of bilberry (Vaccinium myrtillus L.) in Finland.J. Agric. Food Chem.,56,190-196.
30. LaVail, M.M.,Gorrin, G.M.,Repaci, M.A.(1987).Strain differences in sensitivity to light-induced photoreceptor degeneration in albino mice.Curr. Eye Res.,6,825-834.
31. Li, W.,Yin, X.,Zhang, C.,Li, L.,Wang, L.,Xiao, Y.(2009).Comparative study between Cassia obtusifolia and processed Cassia obtusifolia on anti-oxidation effect and NO/ET secretion.Zhongguo Zhong Yao Za Zhi,34,2383-2385.
32. Ma, L.,Dou, H.L.,Huang, Y.M.,Lu, X.R.,Xu, X.R.,Qian, F.,Zou, Z.Y.,Pang, H.L.,Dong, P.C.,Xiao, X.,Wang, X.,Sun, T.T.,Lin, X.M.(2012).Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial.Am. J. Ophthalmol.,154,625-634.
33. Ma, L.,Yan, S.F.,Huang, Y.M.,Lu, X.R.,Qian, F.,Pang, H.L.,Xu, X.R.,Zou, Z.Y.,Dong, P.C.,Xiao, X.,Wang, X.,Sun, T.T.,Dou, H.L.,Lin, X.M.(2012).Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration.Ophthalmology,119,2290-2297.
34. Matsunaga, N.,Imai, S.,Inokuchi, Y.,Shimazawa, M.,Yokota, S.,Araki, Y.,Hara, H.(2009).Bilberry and its main constituents have neuroprotective effects against retinal neuronal damage in vitro and in vivo.Mol. Nutr. Food Res.,53,869-877.
35. Miyake, S.,Takahashi, N.,Sasaki, M.,Kobayashi, S.,Tsubota, K.,Ozawa, Y.(2012).Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism.Lab. Invest.,92,102-109.
36. Mozaffarieh, M.,Sacu, S.,Wedrich, A.(2003).The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence.Nutr. J.,2,20.
37. Muth, E.R.,Laurent, J.M.,Jasper, P.(2000).The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity.Altern. Med. Rev.,5,164-173.
38. Mykkanen, O.T.,Kalesnykas, G.,Adriaens, M.,Evelo, C.T.,Torronen, R.,Kaarniranta, K.(2012).Bilberries potentially alleviate stress-related retinal gene expression induced by a high-fat diet in mice.Mol. Vis.,18,2338-2351.
39. Oyaizu, M.(1986).Studies on products of browning reaction. Antioxidative activities of products of browning reaction prepared from glucosamine.Jpn. J. Nutr. Diet.,44,307-315.
40. Parente, L.M.,Lino Junior Rde, S.,Tresvenzol, L.M.,Vinaud, M.C.,de Paula, J.R.,Paulo, N.M.(2012).Wound healing and antiinflammatory effect in animal models of Calendula officinalis L. growing in Brazil.Evid. Based Complement. Alternat. Med.,2012,375671.
41. Peng, Y.,Ma, C.,Li, Y.,Leung, K.S.,Jiang, Z.H.,Zhao, Z.(2005).Quantification of zeaxanthin dipalmitate and total carotenoids in Lycium fruits (Fructus Lycii).Plant Foods Hum. Nutr.,60,161-164.
42. Perche, O.,Doly, M.,Ranchon-Cole, I.(2007).Caspase-dependent apoptosis in light-induced retinal degeneration.Invest. Ophthalmol. Vis. Sci.,48,2753-2759.
43. Petsalo, A.,Jalonen, J.,Tolonen, A.(2006).Identification of flavonoids of Rhodiola rosea by liquid chromatography-tandem mass spectrometry.J. Chromatogr. A,1112,224-231.
44. Preethi, K.C.,Kuttan, R.(2009).Wound healing activity of flower extract of Calendula officinalis.J. Basic Clin. Physiol. Pharmacol.,20,73-79.
45. Raal, A.,Kirsipuu, K.,Must, R.,Tenno, S.(2009).Content of total carotenoids in Calendula officinalis L. from different countries cultivated in Estonia.Nat. Prod. Commun.,4,35-38.
46. Rapp, L.M.,Maple, S.S.,Choi, J.H.(2000).Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina.Invest. Ophthalmol. Vis. Sci.,41,1200-1209.
47. Renaud, R.C.,Xuereb, H.(2003).Vision impairment therapies.Nat. Rev. Drug Discov.,2,425-426.
48. Schriner, S.E.,Avanesian, A.,Liu, Y.,Luesch, H.,Jafari, M.(2009).Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses.Free Radic. Biol. Med.,47,577-584.
49. Shan, X.,Zhou, J.,Ma, T.,Chai, Q.(2011).Lycium barbarum polysaccharides reduce exercise-induced oxidative stress.Int. J. Mol. Sci.,12,1081-1088.
50. Sharma, O.P.,Bhat, T.K.(2009).DPPH antioxidant assay revisited.Food Chem.,113,1202-1205.
51. Takido, M.(1958).Studies on the constituents of the seeds of Cassia obtusifolia L. I. The structure of obtusifolin.Chem. Pharm. Bull.,6,397-400.
52. Wenzel, A.,Grimm, C.,Samardzija, M.,Reme, C.E.(2005).Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration.Prog. Retin. Eye Res.,24,275-306.
53. Widomska, J.,Subczynski, W.K.(2014).Why has nature chosen lutein and zeaxanthin to protect the retina?.J. Clin. Exp. Ophthalmol.,5,326.
54. Xin, Y.F.,You, Z.Q.,Gao, H.Y.,Zhou, G.L.,Chen, Y.X.,Yu, J.,Xuan, Y.X.(2012).Protective effect of Lycium barbarum polysaccharides against doxorubicin-induced testicular toxicity in rats.Phytother. Res.,26,716-721.
55. Yang, M.,Gao, N.,Zhao, Y.,Liu, L.X.,Lu, X.J.(2011).Protective effect of Lycium barbarum polysaccharide on retinal ganglion cells in vitro.Int. J. Ophthalmol.,4,377-379.
56. Yu, M.S.,Ho, Y.S.,So, K.F.,Yuen, W.H.,Chang, R.C.(2006).Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum.Int. J. Mol. Med.,17,1157-1161.
57. Zhang, C.,Lei, B.,Lam, T.T.,Yang, F.,Sinha, D.,Tso, M.O.(2004).Neuroprotection of photoreceptors by minocycline in lightinduced retinal degeneration.Invest. Ophthalmol. Vis. Sci.,45,2753-2759.