Developmental Death of Photoreceptors in the C57BL/6JMouse: Association with Retinal Function and Self-protection

Mervin, Kyle; Stone, Jonathan

doi:10.1006/exer.2002.2063

Cited by 38 publications

(25 citation statements)

References 33 publications

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“…The present results provide evidence that the wave of photoreceptor death which occurs during normal development (from approximately P10 to P26 (Mervin and Stone, 2002)) can be regulated by varying oxygen levels in the retina. Except at the edges of the retina, hypoxia appears to be a factor causing death among photoreceptors during a critical period of their development.…”

Section: Discussionmentioning

confidence: 83%

“…Except at the edges of the retina, hypoxia appears to be a factor causing death among photoreceptors during a critical period of their development. A naturally occurring episode of hypoxia (`physiological hypoxia' (Chan-Ling et al, 1995)), itself the result of accelerating metabolism in photoreceptors, may be the cause of the wave of photoreceptor death which occurs in normal development (preceding paper (Mervin and Stone, 2002)). The present results show that this normally occurring wave of death can be regulated by oxygen, hypoxia accelerating and hyperoxia slowing photoreceptor death, from approximately P12 to P18.…”

Section: Discussionmentioning

confidence: 98%

“…The number of animals studied for normoxia were (as stated in the previous paper (Mervin and Stone, 2002): four at each age except P14 (6 studied), P22 (3) and P26 (3). For hyperoxia and hypoxia, four animals were studied at each age, except the adult, of which seven were studied in hypoxia, none in hyperoxia.…”

Section: Oxygen Exposure and Managementmentioning

confidence: 99%

“…pro®les were counted and analysed as in the previous paper (Mervin and Stone, 2002). Data were taken from normoxic animals (previous paper) and from animals raised from P7 or P8 in hypoxia or hyperoxia.…”

Section: Tunelmentioning

confidence: 99%

“…The death of photoreceptors during normal development of the mouse retina, described in the preceding paper (Mervin and Stone, 2002), begins at about P(postnatal day)12 as their oxidative metabolism accelerates and subsides at about P25, as the survivors express signi®cant levels of the protective factor bFGF. In the rat an analogous period of photoreceptor death occurs between P15 and P25.…”

Section: Introductionmentioning

confidence: 98%

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Regulation by Oxygen of Photoreceptor Death in the Developing and Adult C57BL/6J Mouse

Mervin

Stone

2002

Experimental Eye Research

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 98%

Section: Oxygen Exposure and Managementmentioning

confidence: 99%

Section: Tunelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Regulation by Oxygen of Photoreceptor Death in the Developing and Adult C57BL/6J Mouse

Mervin

Stone

2002

Experimental Eye Research

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Early afferent signaling in the outer plexiform layer regulates development of horizontal cell morphology

Raven

Orton

Nassar

et al. 2007

J of Comparative Neurology

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The dendritic patterning of retinal horizontal cells has been shown to be specified by the cone photoreceptor afferents. The present investigation has addressed whether this specification is due to visually dependent synaptic transmission in the outer plexiform layer or to some other early, pre-visual, neural activity. Individually labeled horizontal cells from dark-reared mice, as well as from mice carrying a mutation in the Cacna1f gene, which encodes the pore-forming calcium channel subunit Ca(v)1.4, were assessed for various morphological features. The dark-reared mice showed no alteration in any of these features, despite showing a compromised maximal voltage response in the electroretinograms. The retinas of Cacna1f mutant mice, by contrast, showed conspicuous morphological changes that mimicked the effects observed previously in coneless transgenic mice. These changes were present as early as postnatal day 10, when the shape and density of the cone pedicles appeared normal. Ultrastructurally, however, the pedicles at this early stage, as well as in maturity, lacked synaptic ribbons and the invaginations associated with postsynaptic processes. These results suggest a role for this calcium channel subunit in ribbon assembly in addition to its role in modulating calcium influx and glutamate release. Together, they suggest a complex cascade of interactions between developing cone pedicles and horizontal cell dendrites involving early spontaneous activity, dendritic attraction, ribbon assembly, and pedicle invagination.

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Systematic spatiotemporal mapping reveals divergent cell death pathways in three mouse models of hereditary retinal degeneration

Power

Rogerson

Schubert

et al. 2019

J of Comparative Neurology

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Calcium (Ca2+) dysregulation has been linked to neuronal cell death, including in hereditary retinal degeneration. Ca2+ dysregulation is thought to cause rod and cone photoreceptor cell death. Spatial and temporal heterogeneities in retinal disease models have hampered validation of this hypothesis. We examined the role of Ca2+ in photoreceptor degeneration, assessing the activation pattern of Ca2+‐dependent calpain proteases, generating spatiotemporal maps of the entire retina in the cpfl1 mouse model for primary cone degeneration, and in the rd1 and rd10 models for primary rod degeneration. We used Gaussian process models to distinguish the temporal sequences of degenerative molecular processes from other variability sources.In the rd1 and rd10 models, spatiotemporal pattern of increased calpain activity matched the progression of primary rod degeneration. High calpain activity coincided with activation of the calpain‐2 isoform but not with calpain‐1, suggesting differential roles for both calpain isoforms. Primary rod loss was linked to upregulation of apoptosis‐inducing factor, although only a minute fraction of cells showed activity of the apoptotic marker caspase‐3. After primary rod degeneration concluded, caspase‐3 activation appeared in cones, suggesting apoptosis as the dominant mechanism for secondary cone loss. Gaussian process models highlighted calpain activity as a key event during primary rod photoreceptor cell death. Our data suggest a causal link between Ca2+ dysregulation and primary, nonapoptotic degeneration of photoreceptors and a role for apoptosis in secondary degeneration of cones, highlighting the importance of the spatial and temporal location of key molecular events, which may guide the evaluation of new therapies.

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Developmental Death of Photoreceptors in the C57BL/6JMouse: Association with Retinal Function and Self-protection

Cited by 38 publications

References 33 publications

Regulation by Oxygen of Photoreceptor Death in the Developing and Adult C57BL/6J Mouse

Regulation by Oxygen of Photoreceptor Death in the Developing and Adult C57BL/6J Mouse

Early afferent signaling in the outer plexiform layer regulates development of horizontal cell morphology

Systematic spatiotemporal mapping reveals divergent cell death pathways in three mouse models of hereditary retinal degeneration

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