Protective effects of lycium barbarum polysaccharides on blood-retinal barrier via ROCK1 pathway in diabetic rats.
Am J Transl Res. 2019 ;11(10):6304-6315. Epub 2019 Oct 15. PMID: 31737184
Lycium barbarum polysaccharides (LBP) is commonly known as a traditional Chinese medicine, which has protective effects against diabetic complications in clinic, such as diabetic retinopathy (DR). Previous studies have revealed that Rho/ROCK pathway play an important role in DR development. However, the mechanism between LBP and DR remains unknown. This study aims to explore the clear mechanism of the protective effect of LBP in diabetic retinopathy. In this study, streptozocin (STZ, 45 mg/kg) was administered for diabetic rats modeling. Weight, blood glucose levels and blood lipid were measured to assess the metabolic changes by LBP on diabetic rats. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption. Hematoxylin and Eosin (HE) staining and immunohistochemistry assay were applied for retina morphology exploration. The membranous disks of retina were examined by transmission electron microscope. Further, high glucose condition was induced in choroidal-retinal endothelial cells (RF/6A). Western blotting was performed for P-Occludin, ROCK1 and P-MLC protein expression. The results indicated that the blood glucose levels, blood lipid and EB infiltration capacity were decreased while the weight was increased in LBP-treated diabetic rats compared with model rats. Moreover, LBP could thicken the overall retina, prevent the disturbance of photoreceptor cell membranous disks and inhibit pathological angiogenesis in diabetes. In addition, the decreased expression of P-Occludin and increased expression of RhoA-associated protein kinase (ROCK) or phosphorylated myosin light chain (P-MLC) were observed in retinal tissue of diabetic rats and high glucose induced by RF/6A cells, which could be rescued by LBP and/or Fasudil. LBP has the protective effects on blood-retinal barrier by regulating the Rho/ROCK signaling pathway in diabetic rats. LBP may be served as a Rho/ROCK inhibitor for the treatment of DR.