Open AccessAnti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy
Author(s) -
Po Lin Liao,
Cheng Hui Lin,
Ching Hao Li,
Chi Hao Tsai,
Jau Der Ho,
George C.Y. Chiou,
Jaw Jou Kang,
Yu Wen Cheng
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep44985
Subject(s) - retinal , diabetic retinopathy , hypoxia (environmental) , blood–retinal barrier , electroretinography , retina , retinopathy , medicine , retinal pigment epithelium , vascular permeability , apoptosis , nitric oxide synthase , fundus photography , diabetes mellitus , fluorescein angiography , ophthalmology , nitric oxide , endocrinology , biology , chemistry , biochemistry , oxygen , organic chemistry , neuroscience
Diabetic retinopathy (DR), a major microvascular complication of diabetes, leads to retinal vascular leakage, neuronal dysfunction, and apoptosis within the retina. In this study, we combined STZ with whole-body hypoxia (10% O 2 ) for quicker induction of early-stage retinopathy in C57BL/6 mice. We also compared the effects of a high glucose condition combined with hypoxia (1% O 2 ) to a low glucose condition by using retinal pigment epithelial (RPE) cells, which are a crucial component of the outer blood-retinal barrier and the damage is related to retinopathy. In the retina of DM/hypoxic C57BL/6 mice, abnormal a-wave and b-wave activity, yellowish-white spots, hyperfluorescence, and reduced retinal thickness were found using electroretinography (ERG), fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Shikonin dose-dependently (0.5–50 mg/kg, per os ) prevented DM/hypoxia-induced lesions. In eye tissue, administration of shikonin also attenuated DM/hypoxia-induced pre-apoptotic protein BAX expression as well as the production of inflammatory proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). We also demonstrated that shikonin administration rescues high glucose/hypoxia (1% O 2 )-induced inflammation, decreased junction protein expression, and permeability in RPE cells. These results indicate that shikonin treatment may prevent the loss of vision associated with DR.