Kininogen in autoimmune uveitis: decrease in peripheral blood stream versus increase in target tissue.

This study investigates the role of kininogen in autoimmune uveitis, an incurable eye disease that causes blindness in horses. The research highlights kininogen’s increased presence in afflicted eye tissue and decreased presence in the bloodstream during the disease’s active state, suggesting its potential as an inflammation and neovascularization marker in equine recurrent uveitis.

Research Approach

• The research began with a comparison between the serum proteomes (protein content in the blood) of healthy horses and those with equine recurrent uveitis (ERU), an incurable eye disease. This comparison sought to identify proteins expressed differently between the two groups.
• High-abundance serum proteins were purposefully excluded from the analysis in order to zero in on less common, potentially more significant markers.
• A technique known as 2-D DIGE (Two-Dimensional Difference Gel Electrophoresis) was employed for this comparison. This technique helps map out the protein landscape in a sample, highlighting differences between control and experimental groups.
• The identified candidate proteins were then validated through Western blots and immunohistochemistry in the retina and vitreous of the eye, the target tissues of the disease.

Key Findings

• Out of the ten proteins observed to have different expressions between the healthy and diseased states, five (IgM, IgG4 hc, serotransferrin, alpha-2HS-glycoprotein, and complement factor B) were upregulated (increased their concentration). The other five (albumin, apolipoprotein A-IV and H, IgG5 hc, and high-molecular-weight kininogen (HK)) were downregulated or showed a lower concentration during active uveitis.
• The high-molecular-weight kininogen (HK) showed a lower expression in the blood serum of horses with uveitis, but a significantly higher presence in the afflicted retina and vitreous, the eye regions affected by the disease.
• HKininogen has a known role in inflammation and promoting neovascularization (the formation of new blood vessels), important markers for this disease.
• The study was the first to associate HK with uveitis, revealing coexpression of kininogen and VEGF in inflamed eyes via immunohistochemistry.

Concluding Thoughts

• The researchers suggest that kininogen could serve as a proangiogenic factor in the retina and may shed light on the pathogenesis, or development, of uveitis disease given its dual role in the bloodstream and target tissues during inflammation.
• This discovery supports the pursuit of further research to explore the potential of kininogen as an early-stage or predictive marker for ERU.