The Challenges and Promise of Complement Therapeutics for Ocular Diseases

Front Immunol. 2019 May 15;10:1007. doi: 10.3389/fimmu.2019.01007. eCollection 2019.

Abstract

Ocular inflammation is a defining feature of sight threating diseases and its dysregulation can catalyze and or propagate ocular neurodegenerative maladies such as age-related macular degeneration (AMD). The complement system, an intrinsic component of the innate immunity, has an integral role in maintaining immune-surveillance and homeostasis in the ocular microenvironment; however, overstimulation can drive ocular inflammatory diseases. The mechanism for complement disease propagation in AMD is not fully understood, although there is accumulating evidence showing that targeted modulation of complement-specific proteins has the potential to become a viable therapeutic approach. To date, a major focus of complement therapeutics has been on targeting the alternative complement system in AMD. Recent studies have outlined potential complement cascade inhibitors that might mitigate AMD disease progression. First-in-class complement inhibitors target the modulation of complement proteins C3, C5, factor B, factor D, and properdin. Herein, we will summarize ocular inflammation in the context of AMD disease progression, current clinical outcomes and complications of complement-mediated therapeutics. Given the need for additional therapeutic approaches for ocular inflammatory diseases, targeted complement modulation has emerged as a leading candidate for eliminating inflammation-driven ocular maladies.

Keywords: age-related macular degeneration; complement system; immune modulation; ocular inflammation; therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD59 Antigens / antagonists & inhibitors*
  • CD59 Antigens / metabolism
  • Complement Activation / drug effects
  • Complement Activation / immunology
  • Complement C3 / antagonists & inhibitors*
  • Complement C3 / metabolism
  • Complement C5 / antagonists & inhibitors*
  • Complement C5 / metabolism
  • Complement Factor D / antagonists & inhibitors*
  • Complement Factor D / metabolism
  • Humans
  • Immunity, Innate
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / immunology
  • Macular Degeneration / metabolism
  • Molecular Targeted Therapy / methods*
  • Properdin / antagonists & inhibitors*
  • Properdin / metabolism

Substances

  • CD59 Antigens
  • Complement C3
  • Complement C5
  • CD59 protein, human
  • Properdin
  • Complement Factor D