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Collagen type XII is undetectable in keratoconus Bowman’s layer
  1. Mohammed Rigi1,
  2. Hyeck-Soo Son1,2,
  3. Loren Moon1,
  4. Mario Matthaei3,
  5. Divya Srikumaran1,
  6. Albert S Jun1,
  7. Charles G Eberhart1,
  8. Uri S Soiberman1
  1. 1 Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
  2. 2 Department of Ophthalmology, University Hospital Heidelberg, Heidelberg, Germany
  3. 3 Department of Ophthalmology, University Hospital Cologne, Cologne, Germany
  1. Correspondence to Dr Uri S Soiberman, Johns Hopkins Wilmer Eye Institute, Baltimore, MD 21287, USA; usoiber1{at}jhmi.edu; Dr Charles G Eberhart, Johns Hopkins Wilmer Eye Institute, Baltimore, MD 21287, USA; ceberha{at}jhmi.edu

Abstract

Purpose Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (COL12A1), which localises to Bowman’s layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role of COL12A1 in biomechanical stability, this study aims to characterise COL12A1 expression in all corneal layers involved in KC.

Methods TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally, COL12A1 was knocked out in vitro in immortalised HEK293 cells.

Results COL12A1 expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma.

Conclusions The apparent absence of COL12A1 in KC BL, together with the functional importance that COL12A1 is thought to have in stress bearing areas, suggests that COL12A1 may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to COL12A1 dysregulation in KC.

  • Cornea
  • Pathology
  • Experimental laboratory

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • MR and H-SS contributed equally.

  • Contributors Study conceptualisation: CGE and US. Data collection: MR, H-SS, LM, MM, CGE, and US. Data analysis and interpretation: DS, ASJ, CGE and US. Drafting the manuscript: MR, H-SS, LM and US. Statistical expertise: US. USS is guarantor.

  • Funding Supported by National Eye Institute Grant K08EY027474, an unrestricted departmental grant to Wilmer Eye Institute from Research to Prevent Blindness, and philanthropic grants from Debbie Colson and Jeffrey Williams, Ellen A. Cherniavsky, Hymowitz Family Foundation, Tyrone and Jennifer Throop, the Kahn Foundation, and Donald Jump.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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