The transparent ocular lens is essential for vision because it focuses light onto the retina. Despite recognition of the importance of its unique cellular architecture and mechanical properties, the molecular mechanisms governing these attributes remain elusive. This study aims to elucidate the role of ankyrin-B (AnkB, encoded by ANK2), a membrane scaffolding protein, in lens cytoarchitecture, growth and function using a conditional knockout (cKO) mouse model. The AnkB cKO mouse has no defects in lens morphogenesis but exhibited changes that supported a global role for AnkB in maintenance of lens clarity, size, cytoarchitecture, membrane organization and stiffness. Notably, absence of AnkB led to nuclear cataract formation, which was evident from postnatal day 16. AnkB cKO lens fibers exhibit progressive disruption in membrane organization of the spectrin-actin cytoskeleton, cell adhesion proteins and channel proteins; loss and degradation of several membrane proteins [such as NrCAM. N-cadherin (CDH2) and aquaporin-0 (also known as MIP)]; along with a disorganized plasma membrane and impaired membrane interdigitations. Furthermore, absence of AnkB led to decreased lens stiffness. Collectively, these results illustrate the essential role for AnkB in lens architecture, growth and function through its involvement in membrane skeletal and protein organization and stability.

Keywords:
Ocular lens, Fibers, Membrane organization, Cytoarchitecture, Spectrin, Cataract

Author contributions

Conceptualization: R.M., P.V.R.; Methodology: R.M., A.A., N.P.S.; Validation: R.M., N.P.S., P.V.R.; Formal analysis: R.M., N.P.S., P.V.R.; Resources: P.V.R.; Data curation: R.M., N.P.S., P.V.R.; Writing - original draft: R.M., P.V.R.; Writing - review & editing: R.M., A.A., N.S., P.V.R.; Visualization: R.M., P.V.R.; Supervision: P.V.R.; Project administration: R.M., P.V.R.; Funding acquisition: P.V.R.

Funding

This project was supported by the National Institutes of Health [R01EY034450 and R01EY018590 to P.V.R.; P30EY5722 (core grant)]. Additionally, unrestricted funds came from Research to Prevent Blindness. Deposited in PMC for release after 12 months.

Data availability

All relevant data can be found within the article and its supplementary information.

First Person

This article has an associated First Person interview with the first author of the paper.

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2024
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