Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?

Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (β2GPI) in the plasma of individuals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of β2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H(2)O(2))-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate β2GPI in the retina and choroid of patients with AMD. Free thiol β2GPI is shown to protect the immortalized human RPE cell line against H(2)O(2)-induced cell death, whereas the oxidized form of β2GPI and free thiol bovine serum albumin were not protective. Free thiol β2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol β2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD.