Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus

Study Overview
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Brief Summary
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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.

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

Conditions
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Keratoconus

Intervention / Treatment
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* Procedure: Corneal sampling


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Patients suffering from keratoconus and requiring a first optical corneal transplant | Procedure: Corneal sampling<br>* 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.<br>|
| Controls<br>Patients with an indication of orbital exenteration operation due to an orbital tumor | Procedure: Corneal sampling<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metalloproteinase, Glycoprotein, Cornea, Direct epithelial-stromal interactions, Fibroblasts, Myofibroblasts