Increased homocysteine, homocysteine-thiolactone, protein homocysteinylation and oxidative stress in the circulation of patients with Eales' disease

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 +/- 1.77 mmol/L, P<0.001) and homocysteine-thiolactone (45.3 +/- 6.8 nmol/L, P<0.0001) concentrations were significantly higher compared to homocysteine (11.2 +/- 0.64 mmol/L) and homocysteine-thiolactone (7.1 +/- 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 +/- 0.44 mmol/L, P<0.01) and copper (6.6 +/- 0.42 mmol/L, P<0.001) were lower compared to GSH (8.1 +/- 0.41 mmol/L) and copper (15.4 +/- 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.