Anti-inflammatory properties of shikonin contribute to improved early-stage diabetic retinopathy.
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% O2) 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% O2) 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% O2)-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.
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.|School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan ROC.
Po-Lin
PL
Liao
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan ROC.
Cheng-Hui
CH
Lin
Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.|Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
Ching-Hao
CH
Li
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Chi-Hao
CH
Tsai
Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan, ROC.
Jau-Der
JD
Ho
Institute of Ocular Pharmacology, College of Medicine, Texas A&M Health Science Center, College Station, TX, USA.
George C Y
GC
Chiou
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Jaw-Jou
JJ
Kang
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan ROC.
Yu-Wen
YW
Cheng
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001786:Blood Glucose; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004596:Electroretinography; D004847:Epithelial Cells; D005451:Fluorescein Angiography; D007150:Immunohistochemistry; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D041623:Tomography, Optical Coherence
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D009285:Naphthoquinones; C016101:shikonin