Calcium cell signalling and cataract: role of the endoplasmic reticulum.
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.
Duncan
G
G
School of Biological Sciences, University of East Anglia, Norwich, UK.
Wormstone
I M
IM
D020013:Calcium Signaling / Q000502:physiology*; D002386:Cataract / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006801:Humans; D007908:Lens, Crystalline / Q000254:growth & development