Loss of N-Cadherin from the Endothelium Causes Stromal Edema and Epithelial Dysgenesis in the Mouse Cornea

Vassil Vassilev

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Purpose.: We analyzed the role of N-cadherin in maintaining proper architecture and function of corneal endothelium.

Methods.: To achieve specific removal of N-cadherin from corneal endothelium, we bred mice carrying a floxed N-cadherin gene with those expressing the Cre-recombinase gene under the control of P0 promoter. The corneal structure was analyzed by immunostaining for cell junction proteins as well as by electron microscopy. The apoptotic status was assessed by TUNEL staining. The permeability of corneal endothelium was evaluated using fluorescein dye.

Results.: Removal of endothelial N-cadherin led to the appearance of opacity in the adult corneas. All corneal layers exhibited histological defects: The apical junctional complex (AJC) in corneal endothelium was disorganized, losing the continuity in tight junctions. Collagen fibrils were rearranged in the stroma. The corneal epithelium showed decreased thickness and TUNEL staining revealed increased central areas of apoptosis. Fluorescein dye injection in the anterior chamber confirmed an increased permeability of the endothelial layer. Developmental analysis indicated that, although N-cadherin was lost during embryonic stages, the AJC was maintained normally until early postnatal stages, probably due to the presence of other cadherins at these developmental stages. The junctional defects in endothelial cells, however, became obvious by postnatal day 21 (P21), although stromal and epithelial phenotypes were clearly detectable only in the adult eyes.

Conclusions.: N-cadherin is essential for maintaining proper structure of corneal endothelial AJCs from late postnatal to adult stages. Its ablation leads to increased endothelial permeability and corneal edema in mature eyes.
Original languageEnglish
JournalInvestigative Opthalmology and Visual Science
Publication statusPublished - Oct 2012

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