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A. Fatima, R. M. Lavker, S. Getsios; Segregation of Ephrin A1 to Discrete Basal Cell Populations of the Ocular Anterior Segmental Epithelia. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2044.
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Ephrin A1 activates EphA receptors on adjacent epithelial cells. This juxtaposition of ligand/receptor helps establish functional boundaries between distinct cell populations and maintains the gut epithelial stem cell compartment. To begin to understand the role of ephrin A1 in organizing cellular compartments of the eye, we examined its distribution in the anterior segmental epithelia.
Immunostaining, immunoblotting and RT-PCR techniques were used to examine ephrin A1 and EphA2 in mouse/human eyes and primary human corneal keratinocytes (HCKs).
Ephrin A1 was restricted to basal cells in conjunctival, mucocutaneous junctional (MCJ), meibomian gland ductal and limbal epithelia. Ephrin A1 was not expressed in the more differentiated suprabasal epithelial cells, conjunctival goblet cells or central corneal epithelium. Presence of ephrin A1 in epithelial stem cell-enriched regions led us to examine the distribution of its receptor, EphA2, which is normally found in differentiated epithelial cells. In support of this idea, EphA2 showed a reciprocal expression pattern to ephrin A1 in conjunctival and MCJ epithelia but interestingly was absent from mouse limbal and corneal epithelia. In contrast, EphA2 was abundantly expressed throughout the human corneal epithelium suggesting species-specific differences in corneal EphA receptors. EphA2 expression was further confirmed by immunoblot analysis, which showed the presence of this receptor in HCKs grown in low and high calcium conditions. The absence of EphA2 in mouse cornea prompted us to look for other EphA subtypes. In addition to EphA2, RT-PCR analysis of HCKs revealed the presence of mRNA transcripts for EphA1, EphA4 and EphA8 that may serve as candidate partners for ephrin A1 mediated compartmentalization in mouse eyes.
Reciprocal EphA2/Ephrin A1 expression was noted in the ocular anterior segmental epithelia. The discrete expression pattern noted for Ephrin A1 suggests that this ligand might function normally to help maintain the segregation of progenitor (e.g., limbal basal epithelial) cells from more differentiated (e.g., corneal epithelial) cells.
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