Do calcium channel blockers rescue dying photoreceptors in the Pde6b ( rd1 ) mouse?
Do calcium channel blockers rescue dying photoreceptors in the Pde6b ( rd1 ) mouse?
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DOI：
10.1007/978-1-4419-1399-9_56
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发表时间：
2010
影响因子：
--
通讯作者：
Krizaj, David
中科院分区：
文献类型：
--
作者：
Barabas, Peter;Peck, Carolee Cutler;Krizaj, David
Retinitis pigmentosa (RP) is a genetically heterogeneous set of blinding diseases that affects more than a million people worldwide. In humans, ~5-8% of recessive and dominant RP cases are caused by nonsense mutations in the Pde6b gene coding for the ß-subunit of the rod photoreceptor cGMP phosphodiesterase 6 (PDE6-ß). The study of the disease has been greatly aided by the Pde6brd1 (rd1) mouse model of RP carrying a null PDE6ß allele. Degenerating rd1 rods were found to experience a pathological increase in intracellular calcium concentration (‘Ca overload’) when they enter the apoptotic process at postnatal day 10. A 1999 study suggested that the Ca2+ channel antagonist D-cis diltiazem delays the kinetics of rd1 rod degeneration, conferring partial rescue on scotopic vision. Subsequent reports were mixed: whereas several studies failed to replicate the original results, others appeared to confirm the neuroprotective effects of Ca2+ channel antagonists such as diltiazem, nilvadipine and verapamil. We discuss the discordant results and the controversy they caused, and suggest potential causes for the discrepancy. We also discuss potential involvement of recently identified Ca2+-dependent mechanisms that include protective calcium ATPase mechanisms, ryanodine and IP3 calcium stores, and store operated channels in Pde6brd1 neurodegeneration.
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