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Retinal Degenerative Diseases pp 491–499Cite as

Do Calcium Channel Blockers Rescue Dying Photoreceptors in the Pde6b rd1 Mouse?

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 664))

Abstract

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 Pde6b rd1 (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 of 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 discrepancies between the results of different groups and suggest plausible causes for the discordant results. 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 Pde6b rd1 neurodegeneration.

The authors Peter Barabas and Carolee Cutler Peck equally contributed to this work.

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Acknowledgments

This work was supported by the Knights Templar Eye Foundation, International Retina Research Foundation, Moran TIGER award, the NIH (EY13870), Foundation Fighting Blindness and an unrestricted grant from Research to Prevent Blindness to the Moran Eye Institute. We thank Dr. Wolfgang Baehr for helpful comments. Dr. Barabas wishes to thank Dr. Julianna Kardos and the Chemical Research Center of the Hungarian Academy of Sciences for support.

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA

    Peter Barabas, Carolee Cutler Peck & David Krizaj

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  1. Peter Barabas
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  2. Carolee Cutler Peck
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  3. David Krizaj
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Correspondence to David Krizaj .

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Editors and Affiliations

  1. Health Science Center, University of Oklahoma, Stanton L. Young Blvd. 608, Oklahoma City, 73104, USA

    Robert E. Anderson

  2. Division of Ophthalmology, Cleveland Clinic Foundation, Euclid Ave. 9500, Cleveland, 44195, USA

    Joe G. Hollyfield

  3. School of Medicine, University of California, San Francisco, Kirkham St. 10, San Francisco, 94143, USA

    Matthew M. LaVail

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Barabas, P., Cutler Peck, C., Krizaj, D. (2010). Do Calcium Channel Blockers Rescue Dying Photoreceptors in the Pde6b rd1 Mouse? . In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_56

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