Oxysterol compounds in mouse mutant αA- and αB-crystallin lenses can improve the optical properties of the lens

Wang, Kehao, Hoshino, Masato, Uesugi, Kentaro, Yagi, Naoto, Pierscionek, Barbara K. and Andley, Usha P. (2022) Oxysterol compounds in mouse mutant αA- and αB-crystallin lenses can improve the optical properties of the lens. Investigative Ophthalmology & Visual Science, 63. p. 15. ISSN 1552-5783

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Abstract

Purpose: To investigate how cataract-linked mutations affect the gradient refractive index (GRIN) and lens opacification in mouse lenses and whether there is any effect on the optics of the lens from treatment with an oxysterol compound. Methods: A total of 35 mice including wild-type and knock-in mutants (Cryaa-R49C and Cryab-R120G) were used in these experiments: 26 mice were treated with topical VP1-001, an oxysterol, in one eye and vehicle in the other, and nine mice were untreated controls. Slit lamp biomicroscopy was used to analyze the lens in live animals and to provide apparent cataract grades. Refractive index in the lenses of 64 unfixed whole mouse eyes was calculated from measurements with X-ray phase tomography based on X-ray Talbot interferometry with a synchrotron radiation source. Results: Heterozygous Cryaa-R49C lenses had slightly irregularly shaped contours in the center of the GRIN and distinct disturbances of the gradient index at the anterior and posterior poles. Contours near the lens surface were denser in homozygous Cryab-R120G lenses. Treatment with topical VP1-001, an oxysterol, showed an improvement in refractive index profiles in 61% of lenses and this was supported by a reduction in apparent lens opacity grade by 1.0 in 46% of live mice. Conclusions: These results indicate that α-crystallin mutations alter the refractive index gradient of mouse lenses in distinct ways and suggest that topical treatment with VP1-001 may improve lens transparency and refractive index contours in some lenses with mutations.

Item Type:	Journal Article
Keywords:	refractive index, X-ray, alpha crystallin mutant lenses, oxysterol
Faculty:	Faculty of Health, Education, Medicine & Social Care
Depositing User:	Ian Walker
Date Deposited:	26 Apr 2022 12:40
Last Modified:	31 May 2022 16:18
URI:	https://arro.anglia.ac.uk/id/eprint/707533

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