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Age-related macular degeneration: A disease of extracellular complement amplification
Sarah de Jong1,2, Jiaqi Tang1,2, Simon J Clark1,2,3
1Department for Ophthalmology, University Eye Clinic, Eberhard Karls University of Tübingen, Tübingen, Germany.
Insights
Age-related macular degeneration (AMD) involves complement system activation, damaging the eye. This review explores AMD
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss globally, with increasing incidence due to aging populations.
- No effective treatments currently exist for the majority of AMD patients.
- Genetic and biochemical studies link AMD strongly to the complement system and extracellular matrix remodeling.
Purpose of the Study:
- To review current findings on complement activation in AMD.
- To discuss in vivo observations, cellular models, and pathway synergies in AMD.
- To provide an outlook on clinical trials and future research directions.
Main Methods:
- Review of latest findings on complement activation in AMD.
- Discussion of in vivo human tissue observations.
- Analysis of cellular models and potential pathway synergies.
Main Results:
- Aberrant activation of the complement alternative pathway is observed in AMD patients, both systemically and in ocular tissues.
- Excessive complement activation can lead to host tissue damage, contributing to AMD pathogenesis.
- Evidence suggests a significant role for extracellular matrix remodeling in AMD.
Conclusions:
- The complement system, particularly the alternative pathway, plays a critical role in AMD development and progression.
- Understanding complement dysregulation is key to developing future AMD therapies.
- Ongoing clinical trials offer hope for novel treatment strategies targeting the complement cascade.
Abstract:
Age-related macular degeneration (AMD) is a major cause of vision impairment in the Western World, and with the aging world population, its incidence is increasing. As of today, for the majority of patients, no treatment exists. Multiple genetic and biochemical studies have shown a strong association with components in the complement system and AMD, and evidence suggests a major role of remodeling of the extracellular matrix underlying the outer blood/retinal barrier. As part of the innate immune system, the complement cascade acts as a first-line defense against pathogens, and upon activation, its amplification loop ensures a strong, rapid, and sustained response. Excessive activation, however, can lead to host tissue damage and cause complement-associated diseases like AMD. AMD patients present with aberrant activation of the alternative pathway, especially in ocular tissues but also on a systemic level. Here, we review the latest findings of complement activation in AMD, and we will discuss in vivo observations made in human tissue, cellular models, the potential synergy of different AMD-associated pathways, and conclude on current clinical trials and the future outlook.
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