Related Experiment Videos
Calcium cell signalling and cataract: role of the endoplasmic reticulum
1School of Biological Sciences, University of East Anglia, Norwich, UK.
Abstract:
The lens possesses an impressive array of G-protein receptors that are coupled to the release of intracellular calcium. They include members of the muscarinic, adrenergic and purinergic families and activation of the former has been implicated in cataract for some time. There are several possible mechanisms whereby activation of such receptors could give rise to cataract. A prolonged increase in intracellular calcium would be expected to activate proteases such as calpain and so could induce unscheduled and irreversible breakdown of important structural proteins. It has recently been shown that activation of G-protein receptors also modulates lens cell growth, and any interference with the highly controlled pattern of cell growth and development within the lens is also likely to have catastrophic consequences. If the calcium store is totally inactivated in lens cells, for example by exposure to thapsigargin, then growth ceases. This finding provides a means of inhibiting the lens cell growth which leads to posterior capsular opacification (PCO). For example, it has been shown that thapsigargin-coated intraocular lenses totally inhibit lens cell growth within cultured capsular bags, and if this technology could be transferred to the clinic then it could provide a simple and relatively inexpensive means of preventing PCO.
Insights
Lens G-protein receptors trigger calcium release, potentially causing cataracts. Inhibiting lens cell growth with thapsigargin offers a novel strategy to prevent posterior capsular opacification (PCO).
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- The eye lens contains G-protein receptors linked to intracellular calcium release.
- Muscarinic, adrenergic, and purinergic receptor activation can lead to cataract formation.
- Prolonged calcium increase activates proteases like calpain, degrading structural lens proteins.
Purpose of the Study:
- To investigate the role of G-protein receptors and intracellular calcium in lens function and cataractogenesis.
- To explore the potential of inhibiting lens cell growth for preventing posterior capsular opacification (PCO).
Main Methods:
- Examined G-protein receptor activation and its effect on intracellular calcium levels in lens cells.
- Investigated the impact of calcium store inactivation (using thapsigargin) on lens cell growth.
- Evaluated thapsigargin-coated intraocular lenses in cultured capsular bags.
Main Results:
- G-protein receptor activation modulates lens cell growth.
- Complete inactivation of calcium stores (e.g., with thapsigargin) halts lens cell growth.
- Thapsigargin-coated intraocular lenses effectively inhibited lens cell growth in vitro.
Conclusions:
- Interference with lens cell growth and development can cause cataracts.
- Inhibiting lens cell growth presents a viable strategy for preventing PCO.
- Thapsigargin-coated intraocular lenses show promise for clinical application in PCO prevention.