How does lens cell shape affect the way lenses work?
Research details
- Type of funding: Project Grant
- Grant Holder: Professor Roy Quinlan
- Institute: University of Durham
- Region: North East
- Start date: February 2016
- End Date: May 2019
- Priority: Causes
- Eye Category: Cataract
Overview
Cataracts form when proteins in the lens of the eye build up. But we don’t yet fully understand how the lens normally stays clear (transparent). To find out, the research team have been studying the shape and the structure of the lens.
The cells that make up the lens have an internal scaffolding that holds their shape. And the cell membranes (the ‘skin’ that contains the cell) are studded with channels that let water into and out of the cell. Both the shape of the cells and they let water in and out (their 'permeability') are important for staying clear and for being able to change their focus point (so that we can focus on objects at different distances).
The team has discovered that a protein in the cell’s scaffolding interacts with the water channel protein. And faults in either of the genes that produce these proteins lead to inherited cataract. So in this project, the researchers are studying exactly how the two proteins affect each other and what effect that interaction has on the cell’s shape and how it works. The results will provide the basic information needed to better understand the lens and for future cataract treatment research to build on.
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Scientific summary
Role of BFSP1 in lenticular plasma membrane architecture and the regulation of AQP0
The eye lens is a tissue that embodies the fusion of shape and form with function. The cytoskeleton is one of the major structural elements of lens cells that determine shape and function in the lens, but so do those proteins at the lens plasma membrane. The team has discovered the interaction of a key lens cytoskeletal protein, BFSP1, with an equally important plasma membrane component, AQP0. Mutations in both proteins cause inherited cataract.
Their data show that sequences released from the C-terminal domain of BFSP1 by the action of caspases not only associate with lens fibre cell plasma membranes, but also regulate the calcium sensitivity of AQP0. AQP0 is the major water channel protein in the lens and its activity facilitates lens accommodation, so this interaction with BFSP1 is both very important and very exciting. The mechanism of the association of the C-terminal sequences of BFSP1 with the lens plasma membranes and which of these C-terminal residues are important in the regulation of AQP0 are currently unclear.
In this project the team is working to determine the biophysical properties of the C-terminal BFSP1 fragments, their lipid binding properties, and their effects on both membrane and the calcium sensitive AQP0 water channel properties.