The role of complement system in ocular diseases including uveitis and macular degeneration

Abstract

In the normal eye, the complement system is continuously activated at low levels and both membrane-bound and soluble intraocular complement regulatory proteins tightly regulate this spontaneous complement activation. This allows protection against pathogens without causing any damage to self-tissue and vision loss. The complement system and complement regulatory proteins control the intraocular inflammation in autoimmune uveitis and play an important role in the development of corneal inflammation, age-related macular degeneration and diabetic retinopathy. The evidence derived from both animal models and patient studies support the concept that complement inhibition is a relevant therapeutic target in the treatment of various ocular diseases. Currently, several clinical trials using complement inhibitors are going on. It is possible that, in the near future, complement inhibitors might be used as therapeutic agents in eye clinics.

Figure 1. Complement activation in the development of CNV

Laser photocoagulation results in up-regulation of factor B (↑) expression and decrease in (↓) factor H levels. This causes the activation and amplification of alternative pathway leading to increased deposition of MAC on the cell surface. After laser treatment the expression of CD59 is also down-regulated (↓) causing further loss of regulation (shown with X) and increased formation of MAC. Deposition of MAC results in release of growth factors such as VEGF, TGF-β2 and β-FGF, which leads to the formation of new blood vessels (shown within red circles). Administration of recombinant soluble CD59 (rs CD59) blocks (□) the formation of MAC and this results in inhibition of choroidal angiogenesis