title: Establishment of an in vitro monolayer model of macular corneal dystrophy.
abstract: Macular corneal dystrophy (MCD) is characterized by multiple punctate gray-white opacities in the corneal stromal region, due to the accumulation of abnormally sulfated keratan sulfates. We attempted to develop an in vitro model of MCD by simulating the sulfation inhibition using sodium chlorate, a chemical inhibitor of 3'-phosphoadenosine-5'-phosphosulfate (PAPs). The SEM and micro-Raman spectroscopy results showed the hallmark feature of MCD. Further the gene expression studies elucidated the direct effect of sulfation inhibition on the WNT pathway, that in turn downregulated production of matrix metalloproteinases (MMPs), which causes abnormal matrix deposits leading to loss of transparency in vivo. It also resulted in downregulation of integrin and cadherin complexation that leads to disruption of the epithelial layer in the MCD affected corneas. This study offers a promising initial step toward establishing a relevant in vitro MCD disease model, to assess signaling transduction pathways and devise potential treatment strategies based on MMP administration to the MCD affected corneas.
authors.affiliation: Department of Textile Technology, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Murab
authors.affiliation: Department of Textile Technology, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Shibu
authors.initials: S
authors.lastname: Chameettachal
authors.affiliation: Department of Textile Technology, Indian Institute of Technology Delhi, New Delhi, India.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002704:Chlorates / Q000633:toxicity; D003315:Cornea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D003317:Corneal Dystrophies, Hereditary / Q000378:metabolism / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000633:toxicity; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D063990:Gene Ontology; D006041:Goats; D006540:Herbicides / Q000633:toxicity; D007091:Image Processing, Computer-Assisted; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D055616:Microtechnology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D013430:Sulfate Adenylyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D002704:Chlorates; D004791:Enzyme Inhibitors; D005136:Eye Proteins; D006540:Herbicides; D009097:Multienzyme Complexes; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase; D020782:Matrix Metalloproteinases; C032706:sodium chlorate