Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus (MYKE)

Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus (MYKE)

Keratoconus is characterized by a thinning of the cornea, which causes a decrease in visual acuity due to astigmatism.

Publications suggest that keratoconus is linked to chronic inflammation (increase in pro-inflammatory cytokines and metalloproteinases (MMP). Direct epithelial-stromal interactions (D-ESI) have a role in the induction of metalloproteinases (MMP) and the differentiation of fibroblasts into myofibroblasts via an EMMPRIN membrane glycoprotein (extracellular matrix membran MMP inducer - CD 147). On a healthy cornea, EMMPRIN's effects are prevented by a lack of contact between epithelial and stromal cells through a basement membrane, which is altered in the keratoconus The hypothesis is that stromal thinning of the keratoconus could be related to increased expression of EMMPRIN by epithelial and stromal cells (resulting in increased MMP synthesis), with a preponderance at the most deformed areas.

The main objective is to demonstrate a transformation of fibroblasts to myofibroblasts in the corneal stroma of keratoconus patients.

Study Overview

• Status: Withdrawn
• Conditions: Keratoconus
• Intervention / Treatment: Procedure: Corneal sampling

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Keratoconus patients requiring first optical corneal transplantation and controls with indication of orbital exenteration due to an orbital tumor.

Description

Inclusion Criteria:

• For the cases :

  - Suffering from keratoconus and requiring a first optical corneal transplant

• For the controls:

  • Orbital exenteration operation due to an orbital tumor
  • Absence of any anomaly of the ocular surface observed during the slit lamp examination at the last preoperative consultation

Exclusion Criteria:

• For the cases:

  • Keratoconus patient requiring a tectonic corneal transplant
  • Known pregnancy, or breastfeeding

• For the controls:

  • History of orbital radiotherapy
  • History of corneal surgery
  • History of corneal surface tumour
  • Eye surface abnormality noted in the preoperative period
  • Known keratoconus
  • Known pregnancy, or breastfeeding
  • Secondary exclusion if a keratoconus is diagnosed during the immunohistochemical analysis by visualization of Bowman membrane interruption

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; Patients suffering from keratoconus and requiring a first optical corneal transplant	Procedure: Corneal sampling; Corneal samples will be taken during corneal transplants for cases and orbital exenterations for controls. The mRNA (messenger ribonucleic acid) will be extracted and a retrotranscription will be made to obtain cDNA (complementary DNA). A qPCR (quantitative polymerase chain reaction) will be able to quantify the expression of alpha-SMA, MMP 1-2-3 and 9, and EMMPRIN.
Controls; Patients with an indication of orbital exenteration operation due to an orbital tumor	Procedure: Corneal sampling; Corneal samples will be taken during corneal transplants for cases and orbital exenterations for controls. The mRNA (messenger ribonucleic acid) will be extracted and a retrotranscription will be made to obtain cDNA (complementary DNA). A qPCR (quantitative polymerase chain reaction) will be able to quantify the expression of alpha-SMA, MMP 1-2-3 and 9, and EMMPRIN.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of alpha-SMA's (Smooth Muscle Actin) messenger RNA expression evaluated by quantitative PCR (RT-qPCR) in corneal stroma in keratoconus patients compared to non-keratoconus controls	12 hours

Collaborators and Investigators

• Sponsor: Fondation Ophtalmologique Adolphe de Rothschild

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2019
• Primary Completion (ACTUAL): May 12, 2020
• Study Completion (ACTUAL): May 12, 2020

Study Registration Dates

• First Submitted: June 11, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (ACTUAL): June 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Cornea; Fibroblasts; Glycoprotein; Metalloproteinase; Direct epithelial-stromal interactions; Myofibroblasts
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus
• Other Study ID Numbers: EGN_2017_22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No