Increased levels of intracellular copper stimulate angiogenesis in human umbilical vein endothelial cells (HUVECs). Copper transporter 1 (CTR1) is a copper importer present in the cell membrane and plays a major role in copper transport. In this study, three siRNAs targeting CTR1 mRNA were designed and screened for gene silencing. HUVECs when exposed to 100 µM copper showed 3 fold increased proliferation, migration by 1.8 - fold and tube formation by 1.8 - fold. One of the designed CTR1 siRNA (si 1) at 10 nM concentration decreased proliferation by 2.5 - fold, migration by 4 - fold and tube formation by 2.8 - fold. Rabbit corneal packet assay also showed considerable decrease in matrigel induced blood vessel formation by si 1 when compared to untreated control. The designed si 1 when topically applied inhibited angiogenesis. This can be further developed for therapeutic application.

This report shows that increased vitreous Hcys in PDR and RRD is associated with a significant decrease in LOX-specific activity along with an increase in collagen turnover.

LOX activity showed a statistically significant decrease in the vitreous of PDR and RRD relative to control specimens. This effect can contribute to the inadequate collagen cross-linking that causes the ECM changes that occur in these diseases.

No abstract

Background: Eales' disease (ED) is an idiopathic retinal vascular disorder. It presents with inflammation and neovascularization in the retina. Adult men, aged between 15 and 40 years are more susceptible than women. Homocysteine has been implicated in other ocular diseases including age-related macular degeneration (ARMD), central retinal vein occlusion (CRVO) and optic neuropathy. The present study investigates the role of homocysteine in ED. Methods: Forty male subjects, 20 with ED and 20 healthy controls, were recruited to the study. Their blood samples were used to measure thiobarbituric acid reactive substances (TBARS), glutathione (GSH), homocysteine, homocysteine-thiolactone, extent of homocysteine conjugation with proteins and plasma copper concentration. Results: In the ED group, plasma homocysteine (18.6 AE 1.77 mmol/L, P < 0.001) and homocysteine-thiolactone (45.3 AE 6.8 nmol/L, P < 0.0001) concentrations were significantly higher compared to homocysteine (11.2 AE 0.64 mmol/L) and homocysteine-thiolactone (7.1 AE 0.94 nmol/L) concentrations in control subjects. TBARS (P < 0.011) and protein homocysteinylation (P < 0.030) were higher in the ED group while GSH (5.9 AE 0.44 mmol/L, P < 0.01) and copper (6.6 AE 0.42 mmol/L, P < 0.001) were lower compared to GSH (8.1 AE 0.41 mmol/L) and copper (15.4 AE 0.73 mmol/L) concentrations in control subjects. Conclusions: Increased homocysteine, and its metabolite thiolactone, is associated with the functional impairment of protein due to homocysteinylation in ED.