Abstract

The BTB-kelch protein KLEIP/KLHL20 is an actin binding protein that regulates cell-cell contact formation and cell migration. The aim of our study was to characterize KLEIP's function in ocular health and disease in mice. KLEIP(-/-) mice were generated, and corneas were examined histologically and stained for keratin-1, loricrin, keratin-12, keratin-14, CD31, LYVE-1, F4/80, E-cadherin, and Ki67. Corneal abrasions were performed after eyelid opening. Corneas of KLEIP(+/+) and KLEIP(-/-) mice were indistinguishable at birth. After eyelid opening corneal epithelial hyperplasia started to manifest in KLEIP(-/-) mice, showing a progressive epithelial metaplasia leading to total corneal opacity. In KLEIP(-/-) mice the initial stratified squamous corneal epithelium was altered to an epidermal histo-architecture showing several superficial keratinized cells, cell infiltrations into the stroma, and several apoptotic cells. Skin markers keratin 1 and loricrin were positive, and surface disease was accompanied by deep stromal vascularization. Expression analysis for E-cadherin in KLEIP(-/-) corneas showed acellular areas in the squamous epithelium, indicating a progressive fragile corneal integrity. Removal of the virgin epithelium accelerated strongly development of the epithelial and stromal alterations, identifying mechanical injuries as the major trigger for corneal dystrophy formation and scarification in KLEIP(-/-) mice. The data identify KLEIP as an important molecule regulating corneal epithelial integrity.

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