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

The Challenges and Promise of Complement Therapeutics for Ocular Diseases.

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Department of Ophthalmology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, MA, United States.
Department of Ophthalmology, Harvard Medical School, Boston, MA, United States.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Stellar Chance Laboratories, Philadelphia, PA, United States.


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.


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

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