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Updated: Aug 1, 2026
A Laser-induced Mouse Model of Chronic Ocular Hypertension to Characterize Visual Defects
Published on: August 14, 2013
Development of the visual pathway is disrupted in mice with a targeted disruption of the calcium channel
R J Cork1, Y Namkung, H S Shin
1Department of Cell Biology and Anatomy and the Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Abstract:
Refinement of the retinal pathways to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN) is mediated by nitric oxide (NO). Long-term depression (LTD) can also be induced in SC and LGN during the time at which these pathways are refined, and this LTD is partially dependent on NO and L-type Ca(2+) channel function. In an effort to determine whether NO-mediated pathway refinement is also mediated by Ca(2+) channel function, we have examined the refinement of the retinocollicular and retinogeniculate pathways in mice which lack the gene for the Ca(2+) channel beta(3) subunit (CCKO) and which have significantly reduced L-type Ca(2+) currents. Injections of the anterograde tracer cholera toxin subunit B/HRP were made into one eye of these knockout animals and in wild-type mice ages postnatal day (P) 13, P19, and P26. After 48 hours, mice were perfused and sections processed by using tetramethylbenzidine histochemistry. Labeling distribution in some animals was analyzed quantitatively. Obvious differences in the distribution of the ipsilateral retinocollicular pathway were observed at P15, with the pathway being more exuberant in CCKO mice. This difference was statistically significant. More subtle differences were seen at P21 and P28. Obvious differences were also seen in the contralateral retinogeniculate pathway which in CCKO mice filled most of the domain normally occupied by ipsilateral eye fibers. This difference was also statistically significant. We conclude that reduction in L-type Ca(2+) currents has an effect on axonal refinement similar to that which occurs in NO knockout mice, which supports the possibility that L-type Ca(2+) channel-dependent LTD mediates NO-dependent axonal refinement.
Insights
Nitric oxide (NO) refines visual pathways. Reduced L-type Ca(2+) currents in beta(3) subunit knockout mice mimicked NO-knockout effects, suggesting Ca(2+) channels mediate NO-dependent axonal refinement.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Visual pathway refinement to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN) is crucial for vision.
- Nitric oxide (NO) plays a key role in this developmental process.
- Long-term depression (LTD), influenced by NO and Ca(2+) channels, is implicated in pathway refinement.
Purpose of the Study:
- To investigate the role of Ca(2+) channel function in NO-mediated axonal refinement of visual pathways.
- To determine if L-type Ca(2+) channels are involved in the NO-dependent refinement process.
Main Methods:
- Utilized Ca(2+) channel beta(3) subunit knockout (CCKO) mice with reduced L-type Ca(2+) currents.
- Employed anterograde tracing with cholera toxin subunit B/HRP in CCKO and wild-type mice at postnatal days 13, 19, and 26.
- Analyzed retinocollicular and retinogeniculate pathway labeling distribution using histochemistry and quantitative analysis.
Main Results:
- CCKO mice exhibited significantly more exuberant ipsilateral retinocollicular pathways at P15 compared to wild-type.
- Significant differences in contralateral retinogeniculate pathway organization were observed in CCKO mice.
- These findings indicate that reduced L-type Ca(2+) currents impact axonal refinement.
Conclusions:
- Reduction in L-type Ca(2+) currents affects axonal refinement similarly to NO knockout mice.
- This supports the hypothesis that L-type Ca(2+) channel-dependent LTD mediates NO-dependent axonal refinement.
- Ca(2+) channels are critical components in the NO-mediated developmental sculpting of visual pathways.
