Further Analysis of the Lens of Ephrin-A5-/- Mice: Development of Postnatal Defects

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2013 Feb 13

PMID 23401654

Citations 17

Authors

Alexander I Son

Margaret A Cooper

Michal Sheleg

Yuhai Sun

Norman J Kleiman

Renping Zhou

Affiliations

Soon will be listed here.

Abstract

Purpose: The cells of the mammalian lens must be carefully organized and regulated to maintain clarity. Recent studies have identified the Eph receptor ligand ephrin-A5 as a major contributor to lens development, as mice lacking ephrin-A5 develop abnormal lenses, resulting in cataracts. As a follow-up to our previous study on the cataracts observed in ephrin-A5(-/-) animals, we have further examined the morphological and molecular changes in the ephrin-A5(-/-) lens.

Methods: Wild-type and ephrin-A5(-/-) eyes at various ages were fixed, sectioned, and examined using histological techniques. Protein expression and localization were determined using immunohistochemistry and western blot analysis.

Results: Lens abnormalities in the ephrin-A5(-/-) animals are observed at postnatal stages, with lens opacity occurring by postnatal day 21. Structural defects in the lens are first observed in the outer lens fiber cell region where cells in the ephrin-A5(-/-) lens are severely disorganized. Ephrin-A5 and the Eph receptor EphA2 are expressed during early ocular development and continue to be expressed into postnatal stages. The cataracts in the ephrin-A5(-/-) mutants occur regardless of the presence of the CP49 mutation.

Conclusions: In this follow-up study, we have uncovered additional details explicating the mechanisms underlying ephrin-A5 function in the lens. Furthermore, elucidation of the expression of ephrin-A5 and the Eph receptor EphA2 in the lens supports a fundamental role for this receptor-ligand complex in lens development. These observations, in concert with our previous study, strongly suggest that ephrin-A5 has a critical role in postnatal lens fiber organization to maintain lens transparency.

Citing Articles

Canonical ligand-dependent and non-canonical ligand-independent EphA2 signaling in the eye lens of wild-type, knockout, and aging mice.

Horner J, Vu M, Clark J, Innis I, Cheng C Aging (Albany NY). 2024; 16(20):13039-13075.

PMID: 39466050 PMC: 11552635. DOI: 10.18632/aging.206144.

Deficiency of the bZIP transcription factors Mafg and Mafk causes misexpression of genes in distinct pathways and results in lens embryonic developmental defects.

Patel S, Anand D, Motohashi H, Katsuoka F, Yamamoto M, Lachke S Front Cell Dev Biol. 2022; 10:981893.

PMID: 36092713 PMC: 9459095. DOI: 10.3389/fcell.2022.981893.

Roles of Eph-Ephrin Signaling in the Eye Lens Cataractogenesis, Biomechanics, and Homeostasis.

Murugan S, Cheng C Front Cell Dev Biol. 2022; 10:852236.

PMID: 35295853 PMC: 8918484. DOI: 10.3389/fcell.2022.852236.

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

Cheng C, Wang K, Hoshino M, Uesugi K, Yagi N, Pierscionek B Invest Ophthalmol Vis Sci. 2022; 63(1):2.

PMID: 34978559 PMC: 8742528. DOI: 10.1167/iovs.63.1.2.

Eph-ephrin Signaling Affects Eye Lens Fiber Cell Intracellular Voltage and Membrane Conductance.

Cheng C, Gao J, Sun X, Mathias R Front Physiol. 2021; 12:772276.

PMID: 34899394 PMC: 8656704. DOI: 10.3389/fphys.2021.772276.

References

Van Aken E, Papeleu P, De Potter P, De Laey J, Mareel M . Cadherin expression in the eye. Bull Soc Belge Ophtalmol. 2002; (278):55-9. View

Bassnett S . On the mechanism of organelle degradation in the vertebrate lens. Exp Eye Res. 2008; 88(2):133-9. PMC: 2693198. DOI: 10.1016/j.exer.2008.08.017. View

Shi Y, De Maria A, Bennett T, Shiels A, Bassnett S . A role for epha2 in cell migration and refractive organization of the ocular lens. Invest Ophthalmol Vis Sci. 2011; 53(2):551-9. PMC: 3317406. DOI: 10.1167/iovs.11-8568. View

Grunwald I, Korte M, Adelmann G, Plueck A, Kullander K, Adams R . Hippocampal plasticity requires postsynaptic ephrinBs. Nat Neurosci. 2003; 7(1):33-40. DOI: 10.1038/nn1164. View

Mathias R, Kistler J, Donaldson P . The lens circulation. J Membr Biol. 2007; 216(1):1-16. DOI: 10.1007/s00232-007-9019-y. View

Gao J, Sun X, Martinez-Wittinghan F, Gong X, White T, Mathias R . Connections between connexins, calcium, and cataracts in the lens. J Gen Physiol. 2004; 124(4):289-300. PMC: 2233908. DOI: 10.1085/jgp.200409121. View

Xu L, Overbeek P, Reneker L . Systematic analysis of E-, N- and P-cadherin expression in mouse eye development. Exp Eye Res. 2002; 74(6):753-60. DOI: 10.1006/exer.2002.1175. View

Washburn C, Cooper M, Zhou R . Expression of the tyrosine kinase receptor EphA5 and its ligand ephrin-A5 during mouse spinal cord development. Neurosci Bull. 2007; 23(5):249-55. PMC: 5550571. DOI: 10.1007/s12264-007-0037-7. View

Orsulic S, Kemler R . Expression of Eph receptors and ephrins is differentially regulated by E-cadherin. J Cell Sci. 2000; 113 ( Pt 10):1793-802. DOI: 10.1242/jcs.113.10.1793. View

10.

Kuszak J, Zoltoski R, Sivertson C . Fibre cell organization in crystalline lenses. Exp Eye Res. 2004; 78(3):673-87. DOI: 10.1016/j.exer.2003.09.016. View

11.

Ito M, Yoshioka M . Regression of the hyaloid vessels and pupillary membrane of the mouse. Anat Embryol (Berl). 1999; 200(4):403-11. DOI: 10.1007/s004290050289. View

12.

Jun G, Guo H, Klein B, Klein R, Wang J, Mitchell P . EPHA2 is associated with age-related cortical cataract in mice and humans. PLoS Genet. 2009; 5(7):e1000584. PMC: 2712078. DOI: 10.1371/journal.pgen.1000584. View

13.

Kaul H, Riazuddin S, Shahid M, Kousar S, Butt N, Zafar A . Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family. Mol Vis. 2010; 16:511-7. PMC: 2846848. View

14.

Frisen J, Yates P, McLaughlin T, Friedman G, OLeary D, Barbacid M . Ephrin-A5 (AL-1/RAGS) is essential for proper retinal axon guidance and topographic mapping in the mammalian visual system. Neuron. 1998; 20(2):235-43. DOI: 10.1016/s0896-6273(00)80452-3. View

15.

Son A, Park J, Zhou R . The role of Eph receptors in lens function and disease. Sci China Life Sci. 2012; 55(5):434-43. PMC: 4026180. DOI: 10.1007/s11427-012-4318-7. View

16.

Tan W, Hou S, Jiang Z, Hu Z, Yang P, Ye J . Association of EPHA2 polymorphisms and age-related cortical cataract in a Han Chinese population. Mol Vis. 2011; 17:1553-8. PMC: 3115745. View

17.

Straub B, Boda J, Kuhn C, Schnoelzer M, Korf U, Kempf T . A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells. J Cell Sci. 2003; 116(Pt 24):4985-95. DOI: 10.1242/jcs.00815. View

18.

Gumbiner B . Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 2005; 6(8):622-34. DOI: 10.1038/nrm1699. View

19.

Wride M . Lens fibre cell differentiation and organelle loss: many paths lead to clarity. Philos Trans R Soc Lond B Biol Sci. 2011; 366(1568):1219-33. PMC: 3061109. DOI: 10.1098/rstb.2010.0324. View

20.

Mathias R, White T, Gong X . Lens gap junctions in growth, differentiation, and homeostasis. Physiol Rev. 2010; 90(1):179-206. PMC: 4627646. DOI: 10.1152/physrev.00034.2009. View