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

被引:7
|
作者
Cheng, Catherine [1 ]
Wang, Kehao [2 ]
Hoshino, Masato [3 ]
Uesugi, Kentaro [3 ]
Yagi, Naoto [3 ]
Pierscionek, Barbara [4 ]
机构
[1] Indiana Univ, Sch Optometry, 800 E Atwater Ave, Bloomington, IN 47405 USA
[2] Beihang Univ, Beijing Adv Innovat Ctr Biomed Engn, Sch Engn Med, Key Lab Biomech & Mechanobiol,Minist Educ, Beijing, Peoples R China
[3] Japan Synchrotron Radiat Res Inst Spring 8, 1-1-1 Kouto, Sayo, Hyogo 6795198, Japan
[4] Anglia Ruskin Univ, Fac Hlth Educ Med & Social Care, Med Technol Res Ctr, Chelmsford Campus, Cambridge, England
基金
中国国家自然科学基金;
关键词
GRIN; interdigitation; fiber cells; SEM; ephrin-A5; HUMAN CRYSTALLINE LENS; AGE-RELATED-CHANGES; CONGENITAL CATARACT; 3-DIMENSIONAL ORGANIZATION; TYROSINE KINASE; CELL; STIFFNESS; EPHRIN-A5; GENE; MORPHOLOGY;
D O I
10.1167/iovs.63.1.2
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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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页数:13
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