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Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions

Benjamin J Kim1, Dimitrios C Mastellos2, Yafeng Li1

  • 1Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Progress in Retinal and Eye Research
|December 15, 2020
PubMed

Insights

Age-related macular degeneration (AMD) treatments are lacking for geographic atrophy. Targeting complement system proteins C3 and C5 shows promise for new AMD therapies, offering different inhibition strategies.

Area of Science:

  • Ophthalmology
  • Immunology
  • Biochemistry

Background:

  • Age-related macular degeneration (AMD) causes legal blindness, with geographic atrophy being a key unmet therapeutic need.
  • Complement cascade dysregulation is implicated in AMD pathogenesis.
  • C3 and C5 are central complement components and emerging therapeutic targets for AMD.

Purpose of the Study:

  • To provide a detailed review of C3 and C5 biology in AMD.
  • To critically assess therapeutic strategies targeting C3 and C5.
  • To explore connections between complement, inflammasome, and microglia/macrophage activity in AMD.

Main Methods:

  • Literature review and critical analysis of existing research on C3, C5, and AMD.
  • Discussion of biochemical and structural properties of C3 and C5.
  • Examination of therapeutic approaches targeting C3 and C5.

Main Results:

  • C3 and C5 play critical roles in AMD pathophysiology.
  • Therapeutics targeting C3 offer broad complement inhibition, while C5 inhibitors provide specificity.
  • Understanding C3/C5 interactions with inflammasomes and immune cells is crucial.

Conclusions:

  • Targeting C3 and C5 represents a promising avenue for AMD geographic atrophy treatment.
  • The choice between broad C3 inhibition and specific C5 inhibition requires further investigation.
  • Future research should focus on clarifying C3/C5 biology and its interplay with other inflammatory pathways in AMD.

Keywords:
Age-related macular degenerationC3C5ComplementGeographic atrophyRetina

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