Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization

Corneal neovascularization (CNV) is a sight-threatening condition that is encountered in various inflammatory settings including chemical injury. We recently confirmed that angiopoietin-like protein 2 (ANGPTL2) is a potent angiogenic and proinflammatory factor in the cornea, and we have produced a single-stranded proline-modified short hairpin anti-ANGPTL2 RNA interference molecule that is carried in a lipid nanoparticle (ANGPTL2 Li-pshRNA) for topical application. In this study, we have further examined the topical delivery and anti-ANGPTL2 activity of this molecule and have found that fluorescence-labeled ANGPTL2 Li-pshRNA eye drops can penetrate all layers of the cornea and that ANGPTL2 mRNA expression was dramatically inhibited in both epithelium and stroma at 12 and 24 hours after administration. We also examined the inhibitory effect of ANGPTL2 Li-pshRNA on CNV in a mouse chemical injury model and found that the area of angiogenesis was significantly decreased in corneas treated with ANGPTL2 Li-pshRNA eye drops compared to controls. Together, these findings indicate that this modified RNA interference agent is clinically viable in a topical formulation for use against CNV

Maternal green tea extract intake during lactation attenuates hepatic lipid accumulation in adult male rats exposed to a continuous high-fat diet from the foetal period

Background: Maternal lipid intake in the early postnatal period has a long-term effect on the possibility of fatty liver formation in children; besides, the importance of lipid consumption during lactation for children's health has been suggested. Green tea extract (GTE) contains abundant catechins, and it has been reported to improve lipid metabolism and prevent fatty liver. Objective: The aim of this study was to examine the effects of maternal GTE intake during lactation on hepatic lipid accumulation in adult male rats exposed to a continuous high-fat (HF) diet from the foetal period. Methods: Pregnant Wistar rats received diets containing 13% (control-fat, CON) or 45% (high-fat, HF) fat. CON-fed mothers received the same diet during lactation, whereas HF-fed mothers received either HF diet alone or HF diet supplemented with 0.24% GTE. At weaning, male offspring were divided into three groups, i.e. CON/CON/CON, HF/HF/HF (HF-offspring) or HF/HF+GTE/HF (GTE-offspring), and were fed until 51 weeks. Results: A significant hepatic triglyceride (Tg) accumulation was observed in the HF-offspring when compared with the other offspring. This is presumed to be caused by the promotion of Tg synthesis derived from exogenous fatty acid due to a significant increase in diacylglycerol O-acyltransferase 1 and a decrease in Tg -expenditure caused by decreasing microsomal triglyceride transfer protein (MTTP) and long-chain acyl-CoA dehydrogenase. On the other hand, attenuated hepatic Tg accumulation was observed in the GTE-offspring. The levels of the hepatic lipid metabolism-related enzymes were improved to the same level as the CON-offspring, and particularly, MTTP was significantly increased as compared with the HF-offspring. Conclusion: This study indicates the potential protective effects of maternal GTE intake during lactation on HF diet-induced hepatic lipid accumulation in adult male rat offspring and the possible underlying mechanisms