Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

被引:89
作者
Kowluru, Renu A. [1 ]
Zhong, Qing [1 ]
Santos, Julia M. [1 ]
Thandampallayam, Mangayarkarasi [1 ]
Putt, Doug [1 ]
Gierhart, Dennis L. [2 ]
机构
[1] Wayne State Univ, Kresge Eye Inst, Dept Ophthalmol, Detroit, MI 48202 USA
[2] Zeavision LLC, Chesterfield, MO USA
基金
美国国家卫生研究院;
关键词
Carotenoids; Diabetic retinopathy; Macular pigment; Mitochondria; Nutritional supplements; Zeaxanthin; RETINAL METABOLIC ABNORMALITIES; ENDOTHELIAL GROWTH-FACTOR; MACULAR PIGMENT; OXIDATIVE STRESS; INHIBITION; MITOCHONDRIA; ANTIOXIDANTS; INFLAMMATION; CELLS; RATS;
D O I
10.1186/1743-7075-11-8
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Purpose: Increased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for 'Diabetes Vision Function', on diabetic retinopathy. Methods: Streptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at similar to 4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain), VEGF and inflammatory mediators, interleukin-1 beta and NF-kappa B. Results: Diabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3-4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1 beta and NF-kappa B levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal abnormalities. Conclusions: Nutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators. Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to also inhibit retinopathy, a slow progressing disease feared most by diabetic patients.
引用
收藏
页数:10
相关论文
共 49 条
[1]   Angiogenic pathways in diabetic retinopathy [J].
Aiello, LP .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (08) :839-841
[2]   Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor [J].
Aiello, LP ;
Bursell, SE ;
Clermont, A ;
Duh, E ;
Ishii, H ;
Takagi, C ;
Mori, F ;
Ciulla, TA ;
Ways, K ;
Jirousek, M ;
Smith, LEH ;
King, GL .
DIABETES, 1997, 46 (09) :1473-1480
[3]   Neural apoptosis in the retina during experimental and human diabetes - Early onset and effect of insulin [J].
Barber, AJ ;
Lieth, E ;
Khin, SA ;
Antonetti, DA ;
Buchanan, AG ;
Gardner, TW .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (04) :783-791
[4]  
Busik J, 2009, DIABETES, V58, pA229
[5]   Resistance of retinal inflammatory mediators to suppress after reinstitution of good glycemic control: novel mechanism for metabolic memory [J].
Chan, Pooi-See ;
Kanwar, Mamta ;
Kowluru, Renu A. .
JOURNAL OF DIABETES AND ITS COMPLICATIONS, 2010, 24 (01) :55-63
[6]   Lutein plus Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial [J].
Chew, Emily Y. ;
Clemons, Traci E. ;
SanGiovanni, John Paul ;
Danis, Ronald ;
Ferris, Frederick L., III ;
Elman, Michael ;
Antoszyk, Andrew ;
Ruby, Alan ;
Orth, David ;
Bressler, Susan ;
Fish, Gary ;
Hubbard, Baker ;
Klein, Michael ;
Chandra, Suresh ;
Blodi, Barbara ;
Domalpally, Amitha ;
Friberg, Thomas ;
Wong, Wai ;
Rosenfeld, Philip ;
Agron, Elvira ;
Toth, Cynthia ;
Bernstein, Paul ;
Sperduto, Robert .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2013, 309 (19) :2005-2015
[7]   Effects of modified LDL and HDL on retinal pigment epithelial cells: a role in diabetic retinopathy? [J].
Du, M. ;
Wu, M. ;
Fu, D. ;
Yang, S. ;
Chen, J. ;
Wilson, K. ;
Lyons, T. J. .
DIABETOLOGIA, 2013, 56 (10) :2318-2328
[8]   Photoreceptor cells are major contributors to diabetes-induced oxidative stress and local inflammation in the retina [J].
Du, Yunpeng ;
Veenstra, Alexander ;
Palczewski, Krzysztof ;
Kern, Timothy S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (41) :16586-16591
[9]   Alterations to the Blood-Retinal Barrier in Diabetes: Cytokines and Reactive Oxygen Species [J].
Frey, Tiffany ;
Antonetti, David A. .
ANTIOXIDANTS & REDOX SIGNALING, 2011, 15 (05) :1271-1284
[10]   A central role for inflammation in the pathogenesis of diabetic retinopathy [J].
Joussen, AM ;
Poulaki, V ;
Le, ML ;
Koizumi, K ;
Esser, C ;
Janicki, H ;
Schraermeyer, U ;
Kociok, N ;
Fauser, S ;
Kirchhof, B ;
Kern, TS ;
Adamis, AP .
FASEB JOURNAL, 2004, 18 (10) :1450-+