The keratoconus corneal proteome: Loss of epithelial integrity and stromal degeneration

Raghothama Chaerkady, Hanjuan Shao, Sherri Gae Scott, Akhilesh Pandey, Albert Jun, Shukti Chakravarti

Research output: Contribution to journalArticle

Abstract

Keratoconus is a thinning corneal dystrophy that begins in the early teenage years and ultimately requires cornea transplantation to restore vision. Here we conducted a highly sensitive mass spectrometric analysis of the epithelium and the stroma from keratoconus and normal donor corneas. We identified a total of 932 and 1157 proteins in the consolidated data of the epithelium and stroma, respectively. Technical replicates showed strong correlations (≥. 0.88) in levels of all common proteins, indicating very low technical variations in the data. Analysis of the most increased (≥. 1.5 fold) and decreased (≤. 0.8 fold) proteins in the keratoconus corneal epithelial protein extracts identified proteins related to dermal diseases, inflammation, epithelial stratification and mesenchymal changes. Increased proteins included keratins 6A, 16 and vimentin, while the iron transporter lactotransferrin was decreased. The keratoconus stromal proteome suggests endoplasmic reticular stress, oxidative stress and widespread decreases in many extracellular matrix proteoglycan core proteins, lumican and keratocan, collagen types I, III, V and XII. Marked increase in apoptosis and endocytosis-related proteins suggest degenerative changes in keratocytes, the resident cells of the stroma. This is the most comprehensive proteome analysis of the cornea that highlights similarities of keratoconus with other neurodegenerative diseases. Biological significance: This study provides, to our knowledge, the most comprehensive proteomic analysis of the vision threatening disease keratoconus, which affects a significant portion of the US and global populations. Using iTRAQ and LC/MS/MS, we have identified significant changes in the human corneal epithelium and stromal proteome that correlate to in vivo clinical findings. The protein changes identified will lead to molecular insights into disease pathogenesis and provide candidate genes for genetic studies of keratoconus.

Original languageEnglish (US)
Pages (from-to)122-131
Number of pages10
JournalJournal of Proteomics
Volume87
DOIs
StatePublished - Jul 1 2013

Fingerprint

Keratoconus
Proteome
Proteins
Cornea
Collagen Type XII
Keratin-16
Epithelium
Keratin-6
Neurodegenerative diseases
Corneal Epithelium
Lactoferrin
Oxidative stress
Collagen Type III
Corneal Transplantation
Vimentin
Proteoglycans
Collagen Type I
Endocytosis
Skin Diseases
Neurodegenerative Diseases

Keywords

  • Collagens
  • Cornea
  • ECM
  • Keratoconus
  • Lumican
  • Proteome

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

The keratoconus corneal proteome : Loss of epithelial integrity and stromal degeneration. / Chaerkady, Raghothama; Shao, Hanjuan; Scott, Sherri Gae; Pandey, Akhilesh; Jun, Albert; Chakravarti, Shukti.

In: Journal of Proteomics, Vol. 87, 01.07.2013, p. 122-131.

Research output: Contribution to journalArticle

Chaerkady, Raghothama ; Shao, Hanjuan ; Scott, Sherri Gae ; Pandey, Akhilesh ; Jun, Albert ; Chakravarti, Shukti. / The keratoconus corneal proteome : Loss of epithelial integrity and stromal degeneration. In: Journal of Proteomics. 2013 ; Vol. 87. pp. 122-131.
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