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Publication : EphA2 Affects Development of the Eye Lens Nucleus and the Gradient of Refractive Index.

First Author  Cheng C Year  2022
Journal  Invest Ophthalmol Vis Sci Volume  63
Issue  1 Pages  2
PubMed ID  34978559 Mgi Jnum  J:333860
Mgi Id  MGI:7442381 Doi  10.1167/iovs.63.1.2
Citation  Cheng C, et al. (2022) EphA2 Affects Development of the Eye Lens Nucleus and the Gradient of Refractive Index. Invest Ophthalmol Vis Sci 63(1):2
abstractText  PURPOSE: Our studies in mouse eye lenses demonstrate that ephrin-A5 and EphA2 are needed for normal epithelial cells and lens transparency. We sought to determine whether EphA2 and ephrin-A5 are important for lens morphometrics, nucleus formation, and refractive index. METHODS: We performed tissue morphometric measurements, electron microscopy, Western blots, and interferometric measurements using an X-ray synchrotron beam source to measure the gradient of refractive index (GRIN) to compare mouse lenses with genetic disruption of EphA2 or ephrin-A5. RESULTS: Morphometric analysis revealed that although there is no change in the overall lens volume, there is a change in lens shape in both EphA2-/- lenses and ephrin-A5-/- lenses. Surprisingly, EphA2-/- lenses had small and soft lens nuclei different from hard lens nuclei of control lenses. SEM images revealed changes in cell morphology of EphA2-/- fiber cells close to the center of the lens. Inner EphA2-/- lens fibers had more pronounced tongue-and-groove interdigitations and formed globular membrane morphology only in the deepest layers of the lens nucleus. We did not observe nuclear defects in ephrin-A5-/- lenses. There was an overall decrease in magnitude of refractive index across EphA2-/- lenses, which is most pronounced in the nucleus. CONCLUSIONS: This work reveals that Eph-ephrin signaling plays a role in fiber cell maturation, nuclear compaction, and lens shape. Loss of EphA2 disrupts the nuclear compaction resulting in a small lens nucleus. Our data suggest that Eph-ephrin signaling may be required for fiber cell membrane reorganization and compaction and for establishing a normal GRIN.
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