Smarce1 and Tensin 4 Are Putative Modulators of Corneoscleral Stiffness.

Elizabeth M Boazak,Cassandra M Chu,Rebecca King,Eldon E Geisert,Aaron M Toporek,Jiaxing Wang,C Ross Ethier,Darryl R Overby,Joseph M Sherwood

doi:10.3389/fbioe.2021.596154

Abstract

The biomechanical properties of the cornea and sclera are important in the onset and progression of multiple ocular pathologies and vary substantially between individuals, yet the source of this variation remains unknown. Here we identify genes putatively regulating corneoscleral biomechanical tissue properties by conducting high-fidelity ocular compliance measurements across the BXD recombinant inbred mouse set and performing quantitative trait analysis. We find seven cis-eQTLs and non-synonymous SNPs associating with ocular compliance, and show by RT-qPCR and immunolabeling that only two of the candidate genes, Smarce1 and Tns4, showed significant expression in corneal and scleral tissues. Both have mechanistic potential to influence the development and/or regulation of tissue material properties. This work motivates further study of Smarce1 and Tns4 for their role(s) in ocular pathology involving the corneoscleral envelope as well as the development of novel mouse models of ocular pathophysiology, such as myopia and glaucoma.

Highlights

Corneoscleral stiffness plays a role in multiple ocular pathologies, including glaucoma, myopia, and keratoconus, which together represent important sources of vision loss and blindness
We find seven cis-expression QTLs (eQTLs) and non-synonymous single nucleotide polymorphisms (SNPs) associating with ocular compliance, and show by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunolabeling that only two of the candidate genes, Smarce1 and Tns4, showed significant expression in corneal and scleral tissues
Elevated intraocular pressure (IOP), the primary risk factor for this condition (Leske et al, 2003), deforms optic nerve head tissues, likely accelerating vision loss. Scleral stiffness modulates such optic nerve head deformations (Sigal et al, 2005), and modulating scleral biomechanical properties has been suggested as a novel treatment for glaucoma

Summary

Introduction

Corneoscleral stiffness plays a role in multiple ocular pathologies, including glaucoma, myopia, and keratoconus, which together represent important sources of vision loss and blindness. The pathophysiologies underlying these conditions are poorly understood, and there exists a need for novel therapeutic strategies. Elevated intraocular pressure (IOP), the primary risk factor for this condition (Leske et al, 2003), deforms optic nerve head tissues, likely accelerating vision loss Scleral stiffness modulates such optic nerve head deformations (Sigal et al, 2005), and modulating scleral biomechanical properties has been suggested as a novel treatment for glaucoma.

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