The role of CD24 in age related cataracts
Date
2016
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Age related cataract (ARC) is a leading cause of visual disability. While the environmental determinates of the disease are known, genetics also plays a role, particularly in younger patients. However, the genetic variants that predispose a patient to cataract are not well defined. We have used a combination of bioinformatics and RNA sequencing to define the fiber cell transcriptome in order to predict genes likely to play a role in ARC. We identified a novel gene, CD24, a membrane-associated cell adhesion protein expressed at high levels in immune system and cancer tissues, as a potential mediator of ARC. ☐ In accordance with the bioinformatics tool iSyTE, immunostaining of wildtype lenses with CD24 confirmed that it is expressed from the onset of fiber cell differentiation until adulthood. For the first time, I have shown that CD24 was preferentially expressed in lens fibers, and not in epithelial cells, in mice. Also, CD24 protein might be a clinically relevant candidate in ophthalmology as it is expressed in both the epithelial and fiber cells of human lens tissue. ☐ Morphological analysis using bright field microscopy and refractive analysis using a 200-mesh electron microscopy grid, revealed that CD24 null mouse lenses develop normally, however they exhibit a refractive discontinuity at 4-5 months of age followed by cataract development by 1 year, attenuating their ability to refract light. Ultra-structure analysis using scanning electron microscopy revealed that the fiber cells are disorganized from 6 months onward in CD24 null lenses as opposed to wildtype lenses. Cross sectional staining of CD24 and wheat germ agglutinin (WGA) in wildtype lenses identified that both of them are present more in shorter side of the lens fibers than the broader sides. WGA staining is reduced in CD24 null lens fibers and not in epithelial cells, suggesting that CD24 might be a predominant glycoprotein in the lens fibers. Further studies of the molecular pathways that CD24 participates in to regulate these phenotypes will shed more light on the prevention of age related cataracts.