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Clusterin and complement activation in exfoliation glaucoma.

Ivo Doudevski1, Agueda Rostagno, Mary Cowman

  • 1Department of Pathology, New York University School of Medicine, New York, New York, United States.

Investigative Ophthalmology & Visual Science
|February 20, 2014
PubMed
Summary
This summary is machine-generated.

Clusterin co-localizes with exfoliation deposits, indicating complement system activation in exfoliation glaucoma. This suggests novel therapeutic targets for chronic inflammation in XFS patients.

Keywords:
complement systemexfoliation syndromeextracellular chaperonesprotein misfolding disorders

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Area of Science:

  • Ophthalmology
  • Immunology
  • Biochemistry

Background:

  • Exfoliation syndrome (XFS) is a common cause of secondary glaucoma.
  • The role of clusterin and complement activation in XFS pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the biological significance of clusterin co-localization with exfoliation deposits (XF deposits).
  • To elucidate the role of complement system activation and its pro-inflammatory consequences in exfoliation glaucoma.

Main Methods:

  • High-resolution atomic force microscopy and confocal immunofluorescence were used to analyze XF deposits.
  • ELISA was employed to quantify levels of clusterin, vitronectin, C3a, and soluble C5b-9 in aqueous humor.

Main Results:

  • Atomic force microscopy revealed a dense fibrillar network in XF deposits, with clusterin integral to these fibrils.
  • Significantly elevated levels of complement activation products (C3a, soluble C5b-9) and complement inhibitors (clusterin, vitronectin) were observed in aqueous humor of XFS glaucoma patients.

Conclusions:

  • The findings provide evidence for complement system activation in XFS, generating pro-inflammatory subproducts that may sustain chronic inflammation.
  • Clusterin's association with exfoliation fibrils suggests a potentially overwhelmed chaperone function in response to protein aggregate accumulation.
  • These insights highlight potential novel therapeutic targets for managing inflammation in XFS.