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Analysis of Keratoconus-Related Phenotypes in Two Pcsk1 Mouse Models.

Carol Beatty1, Jingwen Cai2,3, Hongfang Yu2

  • 1Medical College of Georgia, Augusta University, Augusta, GA, USA.

Translational Vision Science & Technology
|February 4, 2026
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Summary

The Pcsk1 gene variant was previously linked to keratoconus (KC). However, Pcsk1 knockout or mutation did not affect corneal phenotype in mouse models, suggesting other factors contribute to KC.

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Area of Science:

  • Ophthalmology and genetics research.
  • Investigating the genetic basis of corneal diseases.

Background:

  • Keratoconus (KC) is a corneal disease influenced by genetic factors.
  • A previous study identified a Pcsk1 gene variant associated with KC in a human family.

Purpose of the Study:

  • To investigate the potential relationship between the Pcsk1 gene and corneal phenotype.
  • To evaluate the effect of Pcsk1 gene alterations on corneal structure and thickness in mouse models.

Main Methods:

  • Two mouse models of Pcsk1 alteration were used: knockout (KO) and N222D point mutation.
  • Central corneal thickness (CCT) and pachymetry were assessed using spectral domain optical coherence tomography (SD-OCT).
  • Corneal morphology was examined via Hematoxylin and eosin (H&E) staining.

Main Results:

  • No significant differences in CCT, pachymetry, or corneal morphology were observed between mutant Pcsk1 mice and their control littermates.
  • Neither the N222D point mutation nor the Pcsk1 KO impacted the corneal phenotype in the studied mouse models.

Conclusions:

  • The Pcsk1 gene, in the context of this study, does not appear to directly cause pathogenic corneal changes.
  • Pcsk1 may contribute to keratoconus development in conjunction with other genetic or environmental factors not examined here.