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Increased ratios of complement factors C3a to C3 in aqueous humor and serum mark glaucoma progression
W H G Hubens1, H J M Beckers2, T G M F Gorgels2
1University Eye Clinic Maastricht, Maastricht Medical Center, Maastricht, the Netherlands; Research School of Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Insights
Complement system activation is increased in progressive primary open angle glaucoma (POAG). Higher complement C3a/C3 ratios in aqueous humor and serum correlate with faster POAG progression, suggesting a role in disease advancement.
Area of Science:
- Ophthalmology
- Immunology
- Proteomics
Background:
- Previous proteomic studies suggest complement system involvement in primary open angle glaucoma (POAG) progression.
- The activity of the complement system in POAG has not been directly assessed.
Purpose of the Study:
- To investigate the role of complement system activation in the progression of POAG.
- To compare complement activation levels in aqueous humor and serum of POAG patients with controls.
Main Methods:
- Collected aqueous humor (AH) and serum from 30 patients (10 progressive POAG, 10 stable POAG, 10 cataract controls).
- Measured complement factors C3 and C3a using ELISA kits.
- Calculated the C3a/C3 ratio as an indicator of complement cascade activation.
Main Results:
- Progressive POAG patients showed significantly elevated serum C3a levels compared to controls.
- The C3a/C3 ratio was significantly higher in both AH and serum of progressive POAG patients.
- A strong correlation was found between the C3a/C3 ratio and the rate of glaucoma disease progression in both body fluids.
Conclusions:
- Complement system activation is elevated in progressive POAG.
- The C3a/C3 ratio serves as a reliable indicator of POAG progression.
- Systemic changes in complement activation may be associated with POAG progression.
Introduction:
We recently performed a combined analysis of publicly available proteomic studies of aqueous humor (AH) of patients with primary open angle glaucoma (POAG). This analysis revealed changes in complement protein concentrations in the AH of progressive POAG patients, which suggested that the complement system may play a role in POAG progression. As the proteomic studies could not provide information on the activity of the complement system, we addressed this question in the current study.
Methods:
Blood serum and AH were obtained from 30 patients: 10 progressive POAG, 10 stable POAG and, as controls, 10 cataract patients. Glaucoma patients with a visual field Mean Deviation (MD) change of at least 1.0 dB/year were considered progressive; a MD change of less than 0.5 dB/year was considered stable. The ratio between the levels of complement factors C3a and C3 was used as indicator for activation of the complement cascade. The factors were measured with commercially available ELISA kits.
Results:
AH levels of complement factors C3 and C3a did not significantly differ between groups. In serum, complement factor C3 did not differ between groups whereas C3a was significantly elevated in progressive POAG patients compared to controls (p < 0.05). The resulting complement C3a/C3 ratio was significantly higher in progressive POAG patients in both AH (p < 0.05) and serum (p < 0.01), and this ratio significantly correlated between the two body fluids (p < 0.001). Furthermore, there was a strong correlation between disease progression and C3a/C3 activation ratio both in AH (p < 0.01) and in serum (p < 0.001). The higher the complement C3a/C3 ratio, the faster the disease progression.
Conclusion:
Significant increases in AH and serum complement C3a/C3 ratios were observed in progressive POAG patients but not in stable POAG patients. Furthermore, the complement C3a/C3 ratio correlated strongly with the rate of disease progression in both AH and serum. These findings suggest that activation of the complement system plays a role in glaucoma progression and that progressive glaucoma patients may have systemic changes in complement activation.
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