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Dietary wolfberry ameliorates retinal structure abnormality through activation of AMP activated protein kinase signaling in the db/db type 2 diabetic mouse
Author(s) -
Lin Dingbo,
Tang Ling,
Jiang Yu,
Willard Lloyd,
Ortiz Edlin,
Medeiros Denis M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.224.4
Subject(s) - abnormality , protein kinase a , retinal , endocrinology , medicine , signal transduction , kinase , chemistry , ophthalmology , biochemistry , psychiatry
Objective To determine the protective effect of dietary wolfberry on retinal abnormality in the db/db mouse at the early stage of type 2 diabetes. Methods db/db mice at the age of 6 weeks were fed low fat diet with or without supplemental 1 kCal % wolfberry for 8 weeks. Human retinal pigment epithelial ARPE‐19 cells were exposed to high glucose to mimick hyperglycemia in vitro. Retinal structure was investigated by light microscopy. Alteration of protein expression was monitored by Western blot. siRNA was used to knockdown AMPKα in ARPE‐19 cells. Results Dietary wolfberry restored thickness of whole retina, in particular the photoreceptor layer, and integrity of retinal pigment epithelia (RPE). Addition of wolfberry lowered expression of endoplasmic reticulum stress biomarkers BiP, PERK, ATF6, and caspase‐12; restored AMPKα, thioredoxin, Mn SOD, and FOXO3α activities. Zeaxanthin mimicked wolfberry preventive effect on AMPKα activation and normalization of reactive oxygen species in ARPE‐19 cells exposed to high glucose challenge. Zeaxanthin preventive effect was abolished by siRNA knockdown of AMPKα. Conclusions Dietary wolfberry restoration of AMPKα led to enhanced expression of thioredoxin and Mn SOD, which, in turn, resulted in mitigation of cellular oxidative stress and subsequent prevention of retinal disorganization in the retina of db/db mice at the early stage of type 2 diabetes. Supported by NIH COBRE Grant P20‐RR‐017686 (to D.L.)