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The Complement Pathway

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The Complement Pathway Is Pivotal

Dysregulation of the complement pathway has been strongly associated with the progression and pathogenesis of geographic atrophy (GA).1,2

Find out about the role of each complement protein in the pathway below.

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C3 convertase

All 3 complement pathways converge at the C3 convertase enzyme1

C3

C3 convertase cleaves C3 to form C3a, which has proinflammatory effects through inflammasome activation, and C3b, which plays a role in pathogen opsonization and can be beneficial for anti-inflammatory activities1-3

C5 convertase

As C5 convertase cleaves C5 into C5a and C5b, it initiates the terminal cascade of the complement system1

C5a

Can lead to inflammation, causing death of retinal pigment epithelial cells1,4,5

C5b

Initiates cell death through the membrane attack complex (MAC)6

Watch and Discover: GA and the Complement Pathway

Learn more about the complement pathway and its role in the pathogenesis of GA. 

References

  1. Boyer DS, Schmidt-Erfurth U, van Lookeren Campagne M, Henry EC, Brittain C. The pathophysiology of geographic atrophy secondary to age-related macular degeneration and the complement pathway as a therapeutic target. Retina. 2017;37(5):819-835.
  2. Xu H, Chen M. Targeting the complement system for the management of retinal inflammatory and degenerative diseases. Eur J Pharmacol. 2016;787:94-104.
  3. Coulthard LG, Woodruff TM. Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. J Immunol. 2015;194(8):3542-3548.
  4. Xie CB, Jane-Wit D, Pober JS. Complement membrane attack complex: new roles, mechanisms of action, and therapeutic targets. Am J Pathol. 2020;190(6):1138-1150.
  5. Brandstetter C, Holz FG, Krohne TU. Complement component C5a primes retinal pigment epithelial cells for inflammasome activation by lipofuscin-mediated photooxidative damage. J Biol Chem. 2015;290(52):31189-31198.
  6. Kumar-Singh R. The role of complement membrane attack complex in dry and wet AMD - from hypothesis to clinical trials. Exp Eye Res. 2019;184:266-277.