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Shivalingappa K. Swamynathan, Doreswamy Kenchegowda, Divya Gupta, Sudha Swamynathan, Huajing Wan, Jeffrey Whitsett, Joram Piatigorsky; Conditional Disruption of Mouse Klf5 Results in Defective Eyelids with Malformed Meibomian Glands, Abnormal Cornea and Loss of Conjunctival Goblet Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2585.
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Previously, we have demonstrated the role of the Krüppel-like transcription factor Klf4 in ocular surface development. Here, we have examined the functions of the structurally related transcription factor Klf5, also highly expressed in the mouse cornea.
Klf5-conditional null (Klf5CN) mice were generated by breeding Klf5-LoxP with Le-Cre mice. Hematoxylin-eosin, Periodic acid-Schiff’s (PAS) reagent and oil red-O stains were used to examine the histology, conjunctival goblet cells and the meibomian gland lipid production, respectively. Immunofluorescence with anti-CD31, anti-CD45 and anti-Ki67 antibody was used to evaluate neovascularization, immune cell infiltration and cell proliferation, respectively.
Expression of Klf5, observed in the wild type ocular surface as early as embryonic day 12, increased as development progressed and was successfully abrogated in the Klf5CN ocular surface. Embryonic development of the Klf5CN eyes including the eyelid fusion appeared normal. However, postnatal maturation of the Klf5CN eyes was severely affected, resulting in smaller eyeballs, swolleneyelids with malformed meibomian glands and translucent cornea. The Klf5CN corneal epithelial basement membrane was less intensely stained with PAS reagent. The Klf5CN stroma was edematous with signs of neovascularization, hypercellularity and inflammation. The Klf5CN conjunctiva lacked mucin producing goblet cells. The Klf5CN ocular surface epithelial cells were hyperproliferative, judged by the increased numbers of Ki67-positive cells.
Klf5 is an integral component of the genetic network regulating postnatal development of the anterior eye. We suggest that the Klf5CN mouse is a useful model for investigating the ocular surface pathologies associated with corneal neovascularization, meibomian gland dysfunction, blepharitis and loss of conjunctival goblet cells.
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