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Differential analysis of core complement components expression and localization across rodent, non-human primate, and
Aarin Jones1, Aixu Sun1, Hua Yang1
1Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.
Experimental Eye Research
|May 26, 2025
Summary
Complement factor distribution in ocular tissues differs significantly across species, impacting age-related macular degeneration (AMD) research. Understanding these variations is crucial for developing effective AMD therapeutics.
Area of Science:
- Ocular immunology
- Complement biology
- Translational medicine
Background:
- Age-related macular degeneration (AMD) is a leading cause of blindness.
- Complement pathway dysfunction is implicated in AMD pathogenesis.
- Limited success of anti-complement therapeutics in clinical trials may stem from species-specific complement biology.
Purpose of the Study:
- To investigate the expression and localization of key complement components (Factor H, C3, C5) in ocular tissues across species.
- To understand how complement factor distribution varies between rodents, non-human primates, and humans.
- To provide insights into the translatability of animal models for AMD drug development.
Main Methods:
- Integrated transcriptomic and immunohistochemical assays.
- Analysis of ocular tissues from rodent, non-human primate, and human species.
- Quantification and localization of complement factor H (FH), complement 3 (C3), and complement 5 (C5).
Main Results:
- Significant species-specific differences in complement distribution were observed, particularly for FH.
- Rodent FH was mainly expressed in the RPE, while primate FH was found in the choroid.
- C3 mRNA and protein showed similar distribution in the choroid across species; C5 protein was detected in RPE (rodents) and choroid (humans).
Conclusions:
- Key differences and similarities in ocular complement biology exist between rodents and primates.
- These findings may explain the limited success of anti-complement therapies in clinical trials.
- Understanding species-specific complement localization is vital for designing effective AMD therapeutics and improving animal model translatability.
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