Related Experiment Video
Updated: Jun 15, 2026
Imaging Ca2+ Dynamics in Cone Photoreceptor Axon Terminals of the Mouse Retina
Published on: May 6, 2015
Do calcium channel blockers rescue dying photoreceptors in the Pde6b ( rd1 ) mouse?
Peter Barabas1, Carolee Cutler Peck, David Krizaj
1Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
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 Ca(2+) 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 Ca(2+) 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 Ca(2+)-dependent mechanisms that include protective calcium ATPase mechanisms, ryanodine and IP3 calcium stores, and store operated channels in Pde6b ( rd1 ) neurodegeneration.
Insights
Calcium channel blockers may offer partial rescue for retinitis pigmentosa (RP) by slowing degeneration in Pde6b (rd1) mouse models. Discrepancies in studies highlight the need for further research into calcium-dependent mechanisms in RP.
Area of Science:
- Ophthalmology
- Genetics
- Neuroscience
Background:
- Retinitis pigmentosa (RP) is a group of blinding diseases affecting over a million people globally.
- Nonsense mutations in the Pde6b gene cause ~5-8% of human RP cases, affecting the rod photoreceptor cGMP phosphodiesterase 6 (PDE6-ss) subunit.
- The Pde6b (rd1) mouse model with a null PDE6ss allele aids RP research.
Purpose of the Study:
- To investigate the neuroprotective effects of calcium (Ca2+) channel antagonists on Pde6b (rd1) mouse model degeneration.
- To explore the reasons for conflicting results in previous studies on Ca2+ channel blockers in RP models.
- To examine the role of various Ca2+-dependent mechanisms in Pde6b (rd1) neurodegeneration.
Main Methods:
- Utilized the Pde6b (rd1) mouse model of retinitis pigmentosa.
- Examined the effects of Ca2+ channel antagonists (e.g., D-cis diltiazem, nilvadipine, verapamil) on rod degeneration kinetics.
- Reviewed and analyzed existing literature to identify causes for discrepancies in experimental outcomes.
Main Results:
- Early studies suggested D-cis diltiazem partially rescues scotopic vision by delaying rd1 rod degeneration.
- Subsequent research yielded mixed results, with some studies confirming neuroprotective effects of Ca2+ channel antagonists and others failing to replicate findings.
- Identified potential Ca2+-dependent mechanisms, including calcium ATPases, ryanodine and IP3 stores, and store-operated channels, as relevant to Pde6b (rd1) neurodegeneration.
Conclusions:
- Conflicting results regarding the efficacy of Ca2+ channel antagonists in RP models necessitate further investigation.
- Understanding the complex interplay of Ca2+-dependent pathways is crucial for developing effective treatments for Pde6b (rd1) related RP.
- The study highlights the potential therapeutic avenues involving modulation of intracellular calcium homeostasis in photoreceptor degeneration.
