Understanding lens cell regeneration
- Type of funding: Project Grant
- Grant Holder: Professor Roy Quinlan
- Institute: University of Durham
- Region: North East
- Start date: January 2012
- End Date: December 2014
- Eye Category:
Cataract surgery involves removing a clouded lens (cataract) from the eye and replacing it with a clear artificial lens. But some cells from the original lens will always remain. In time, these cells can grow across the back of the artificial lens, making vision hazy again. This is known as ‘posterior capsule opacification’ or PCO. It’s the most common complication of cataract surgery.The research team has discovered that, instead of replacing the lens, it may be possible to get the lens to regrow, using a different surgical technique. So in this project they are studying both PCO and lens regeneration as they are thought to be two different results of a shared wound-healing process by lens cells. They are trying to understand what happens to cells and the molecules inside them to trigger each process with the aim of improving cataract treatment.
Harnessing lens regeneration to control posterior capsule opacification and enable the next and future generations of intraocular lensesThe team aims to determine the cellular and expression signatures for rat lens regeneration. Mammals can regenerate an optically functional lens after removal of the fibre mass. This positive outcome contrasts posterior capsule opacification (PCO), which results when the capsulorhexis is removed during surgery. The team has developed both models in rat.
PCO is a major obstacle to deploying new accommodative intraocular (IOL) lenses. Yet the rat models suggest that PCO can be averted if regeneration is encouraged by re-establishing the lens-capsule barrier. To test this hypothesis, the process of regeneration at the cellular level and how this differs to PCO must be detailed.
EdU labelling at different times over the first two weeks and immunohistochemistry of flat-mounted rat lens epithelia, will identify the cells and their capsule location in each model. This will inform both the lens stem cell debate and how progenitors and their cell progeny regenerate an adult lens, important issues if regeneration is to compliment IOL technology.
The expression profile for lens epithelial cells during the first few weeks of regeneration will be compared to PCO. qRT-PCR followed by immunoblotting and immunohistochemistry of selected genes and their products will be used to validate these data and identify the pathways and their regulators that encourage regeneration. Lastly the team is assessing how IOLs, hydrogel-based implants and growth factor-impregnated dynamic-release hydrogels affect lens regeneration as a first step to demonstrating the potential clinical application of lens regeneration to combat PCO.
In this project the team has studied lens cell regeneration in mammals, using their measurements to build a mathematical model of how lenses grow and re-grow. This is very useful for understanding and being able to predict the effects of potential new ways to treat cataract.
- Wu JJ, Wu W, Tholozan FM, Saunter CD, Girkin JM, Quinlan RA. A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens. Journal of The Royal Society Interface . 2015 Jul 6 ;12(108):20150391.
- Markiewicz E, Barnard S, Haines J, Coster M, Geel O van, Wu W, et al. Nonlinear ionizing radiation-induced changes in eye lens cell proliferation, cyclin D1 expression and lens shape. Open Biology. 2015 Apr 1 ;5(4):150011
- Wu W, Tholozan FM, Goldberg MW, Bowen L, Wu J, Quinlan RA. A gradient of matrix-bound FGF-2 and perlecan is available to lens epithelial cells. Exp Eye Res. 2014 Mar;120:10–4.