The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis

Abstract

Age-related macular degeneration is a retinal disease that causes permanent loss of central vision in people over the age of 65. Its pathogenesis may be related to mitochondrial dysfunction, inflammation, apoptosis, autophagy, complement, intestinal flora, and lipid disorders. In addition, the patient's genes, age, gender, cardiovascular disease, unhealthy diet, and living habits may also be risk factors for this disease. Complement proteins are widely distributed in serum and tissue fluid. In the early 21st century, a connection was found between the complement cascade and age-related macular degeneration. However, little is known about the effect of complement factors on the pathogenesis of age-related macular degeneration. This article reviews the factors associated with age-related macular degeneration, the relationship between each factor and complement, the related functions, and variants and provides new ideas for the treatment of this disease.

Figure 1

The classical pathway and the MBL pathway activate C1 and MBL-MASP-2, respectively, cleaving C2 and C4 to form C3 convertase. C4b2a combines with C3b formed after C3 cleavage to produce C5 convertase. In the alternative pathway, factor B combines with C3b, which is spontaneously hydrolyzed by C3 under the action of factors D and P to generate C3 convertase and C5 convertase. Both of the above enzymes can activate and cleave C5 and participate in the formation of the subsequent MAC.

Figure 2

Changes in complement function accelerate the formation of MAC and activate PI3K, Fas, TNF, and other pathways. Excessive ROS and inflammatory factors are produced in retinal cells, causing cellular mitochondrial dysfunction, oxidative stress, lipid metabolism disorders, inflammatory response, apoptosis, and autophagy response. Studies have shown that changes in the structure of the intestinal flora can also exacerbate the formation of choroidal neovascularization. The combination of the above factors exceeds the compensatory capacity and results in AMD.