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Han na Park, Christopher C. Tan, Robert L. Chow, P. Michael Iuvone, Machelle T. Pardue; Role of Vsx1 in Refractive Development. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4658.
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© ARVO (1962-2015); The Authors (2016-present)
Visual system homeobox1 (Vsx1) is a paired-like homeobox gene that is essential for terminal differentiation of a subset of OFF bipolar cells and the type 7 ON bipolar cell. VSX1 is also a candidate gene for keratoconus and posterior polymorphous corneal dystrophy 1, corneal diseases that are associated with myopia. This study investigates the refractive and ocular development of Vsx1-null mice and its possible links to keratoconus.
Refractive development of Vsx1-null mice was monitored from postnatal day (P) 28 to 112 and compared to age-matched C57BL/6 wild-type mice. Weekly measurements were made of refractive error with an automated infrared photorefractor and corneal radius of curvature (CRC) with an automated infrared keratometer. Ocular parameters were measured using cross-sectional images from 1310 nm spectral-domain optical coherence tomography, including corneal thickness (CT), anterior chamber depth (ACD), posterior chamber depth (PCD), lens thickness (LT), retinal thickness (RT), and axial lengths (AL).
The Vsx1-null mice (n=5) were myopic compared to wild-type mice (n=8) until P105, starting at (-)4.62 ± 2.47 diopters (D) at P28 and shifting to 6.48 ± 1.64D by P112 (Two way RM ANOVA, p <0.001). In comparison, wild-type mice had refractions of 4.56 ± 2.07D at P28 and 7.94 ± 2.35D at P112. Analysis of CRC from P35 to P56 showed significantly flatter CRC in Vsx1-null mice (n=5) compared to the wild-type mice (n=10; Two way RM ANOVA, p=0.012). ACD development showed a steady growth in wild-type mice with age, while Vsx1-null mice had similar ACD throughout development, creating a significant shallower anterior chamber by P63 (Two way RM ANOVA, p<0.001).There were no consistent statistical differences in development of CT, PCD, LT, RT, and AL between the C57BL/6 mice and Vsx1-null mice.
Vsx1-null mice had relatively myopic refractions compared to wild-type mice throughout much of development. The myopic refraction appeared to be caused by the change in CRC and shallower ACD. Since Vsx1 ocular expression has only been detected in the retina, these results would seem to support the role of retinal signaling in controlling the growth of the anterior chamber during refractive development, thus providing a potential link to keratoconus.
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