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Ramachandran Balasubramanian, Melinda K Duncan, Yichen Wang; The role of CD24 in age related cataracts. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Age related nuclear cataract (ARNC) 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 ARNC. This abstract seeks to test the hypothesis that CD24, a membrane-associated cell adhesion protein is expressed at high levels in lens fibers and plays a role in their structure and/or function.
As ARNC affects lens fibers, RNA sequencing analysis was performed in an animal model which fails to make lens fibers which revealed differentially expressed genes (Audette et. al., 2015). CD24 which is a membrane associated glycosylated protein, was found to be expressed in high levels in the lens and this expression was attenuated when fiber cell differentiation was blocked. In order to determine the expression profile of CD24 in wildtype lenses compared to the average expression over the embryo, a bioinformatics tool, iSyTE was utilized. Immunostaining was carried out to confirm the expression of CD24 at various embryonic and adult timepoints. The lenses were subjected to morphological characterization using grid analysis followed by Hematoxylin and Eosin staining. The cortical and nuclear lens fibers of CD24 null and control mice from various timepoints (4, 6, 8, 12 months) were subjected to scanning electron microscopy (SEM).
Immunostaining of wildtype lenses for CD24 and WGA identified that CD24 is a membrane specific fiber cell preferred protein. CD24 knockouts develop a refractive index discontinuity between 5-6 months of age followed by cataract by 1 year, while juvenile lenses were normal with no aberrant phenotype. The SEM revealed that the cortical fiber cells were disorganized while the nuclear fiber cells were intact.
Our data revealed that CD24 is a membrane specific fiber cell preferred gene expressed at high levels from E12.5 till adulthood. CD24 null mice develops a refractive index discontinuity at 5-6 months of age followed by cataract demonstrating that CD24 is an important determinate of fiber cell function.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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