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.

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