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Published on: April 12, 2018
The Complement System Is Critical in Maintaining Retinal Integrity during Aging
Ryo Mukai1,2, Yoko Okunuki1, Deeba Husain1
1Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Harvard University, Boston, MA, United States.
Insights
The complement system is crucial for maintaining retinal health during aging. Its absence leads to decreased retinal function and thinning of the inner nuclear layer in adult mice.
Area of Science:
- Immunology
- Neuroscience
- Ophthalmology
Background:
- The complement system, a vital part of innate immunity, orchestrates proteolytic cascades for cellular clearance.
- While implicated in various inflammatory conditions and focal ocular diseases, its specific role in age-related retinal homeostasis remains unclear.
Purpose of the Study:
- To investigate the role of the complement system in maintaining retinal integrity during aging.
- To assess the impact of complement deficiencies on retinal function and structure in aging mice.
Main Methods:
- Comparative analysis of young and adult wild-type and complement knockout mice (C1q, Mbl a/c, Fb, C3, C5).
- Assessment of retinal function using electroretinograms (ERG).
- Measurement of retinal layer thickness via spectral domain optical coherence tomography (SD-OCT).
Main Results:
- Adult mice with complement deficiencies exhibited significantly decreased ERG amplitudes compared to young counterparts.
- Significant thinning of the inner nuclear layer (INL) was observed in adult complement knockout mice.
- No significant age-related changes in ERG amplitude or INL thickness were found in control mice.
Conclusions:
- The complement system plays a critical role in preserving normal retinal integrity throughout the aging process.
- Complement deficiencies accelerate age-related functional and structural decline in the retina.
- These findings highlight the complement system as a potential target for age-related retinal diseases.
Abstract:
The complement system is a key component of innate immunity comprised of soluble components that form a proteolytic cascade leading to the generation of effector molecules involved in cellular clearance. This system is highly activated not only under general inflammatory conditions such as infections, collagen diseases, nephritis, and liver diseases, but also in focal ocular diseases. However, little is known about the role of the complement system in retinal homeostasis during aging. Using young (6-week-old) and adult (6-month-old) mice in wild type (C57BL/6) and complement knockout strains (C1q-/-, Mbl a/c-/-, Fb-/-, C3-/-, and C5-/-), we compared amplitudes of electroretinograms (ERG) and thicknesses of retinal layers in spectral domain optical coherence tomography between young and adult mice. The ERG amplitudes in adult mice were significantly decreased (p < 0.001, p < 0.0001) compared to that of young mice in all complement knockout strains, and there were significant decreases in the inner nuclear layer (INL) thickness in adult mice compared to young mice in all complement knockout strains (p < 0.0001). There were no significant differences in ERG amplitude or thickness of the INL between young and adult control mice. These data suggest that the complement system plays an important role in maintaining normal retinal integrity over time.
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