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Outer Nuclear Layer (outer + nuclear_layer)
Selected AbstractsGenetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retinaDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2008Ann C. Morris Abstract Development of therapies to treat visual system dystrophies resulting from the degeneration of rod and cone photoreceptors may directly benefit from studies of animal models, such as the zebrafish, that display continuous retinal neurogenesis and the capacity for injury-induced regeneration. Previous studies of retinal regeneration in fish have been conducted on adult animals and have relied on methods that cause acute damage to both rods and cones, as well as other retinal cell types. We report here the use of a genetic approach to study progenitor cell responses to photoreceptor degeneration in the larval and adult zebrafish retina. We have compared the responses to selective rod or cone degeneration using, respectively, the XOPS-mCFP transgenic line and zebrafish with a null mutation in the pde6c gene. Notably, rod degeneration induces increased proliferation of progenitors in the outer nuclear layer (ONL) and is not associated with proliferation or reactive gliosis in the inner nuclear layer (INL). Molecular characterization of the rod progenitor cells demonstrated that they are committed to the rod photoreceptor fate while they are still mitotic. In contrast, cone degeneration induces both Müller cell proliferation and reactive gliosis, with little change in proliferation in the ONL. We found that in both lines, proliferative responses to photoreceptor degeneration can be observed as 7 days post fertilization (dpf). These two genetic models therefore offer new opportunities for investigating the molecular mechanisms of selective degeneration and regeneration of rods and cones. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Time course analysis of gene expression during light-induced photoreceptor cell death and regeneration in albino zebrafishDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2007Sean C. Kassen Abstract Constant intense light causes apoptosis of rod and cone photoreceptors in adult albino zebrafish. The photoreceptors subsequently regenerate from proliferating inner nuclear layer (INL) progenitor cells that migrate to the outer nuclear layer (ONL) and differentiate into rods and cones. To identify gene expression changes during this photoreceptor regeneration response, a microarray analysis was performed at five time points during the light treatment. The time course included an early time point during photoreceptor death (16 h), later time points during progenitor cell proliferation and migration (31, 51, and 68 h) and a 96 h time point, which likely corresponds to the initial photoreceptor differentiation. Mean expression values for each gene were calculated at each time point relative to the control (0 h light exposure) and statistical analysis by one-way ANOVA identified 4567 genes exhibiting significant changes in gene expression along the time course. The genes within this data set were clustered based on their temporal expression patterns and proposed functions. Quantitative real-time PCR validated the microarray expression profiles for selected genes, including stat3 whose expression increased markedly during the light exposure. Based on immunoblots, both total and activated Stat3 protein expression also increased during the light treatment. Immunolocalization of Stat3 on retinal tissue sections demonstrated increased expression in photoreceptors and Müller glia by 16 h of light exposure. Some of the Stat3-positive Müller cells expressed PCNA at 31 h, suggesting that Stat3 may play a role in signaling a subset of Müller cells to proliferate during the regeneration response. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Loss of photic entrainment at low illuminances in rats with acute photoreceptor degenerationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Domitille L. Boudard Abstract In several species, an acute injection of N -methyl- N -nitrosourea (MNU) induces a retinal degeneration characterized principally by a rapid loss of the outer nuclear layer, the other layers remaining structurally intact. It has, however, also been reported that down-regulation of melanopsin gene expression is associated with the degeneration and is detectable soon after injection. Melanopsin is expressed by a small subset of intrinsically photosensitive retinal ganglion cells and plays an important role in circadian behaviour photoentrainment. We injected MNU into Long Evans rats and investigated the ability of animals to entrain to three light/dark cycles of different light intensities (300, 15 and 1 lux). Control animals entrained their locomotor activity rhythms to the three cycles. In contrast, MNU-treated animals could only entrain properly to the 300 lux cycle. For the 15 lux cycle, their phase angle was much altered compared with control animals, and for the 1 lux cycle, MNU-injected animals were unable to photoentrain and exhibited an apparent free-run activity pattern with a period of 24.3 h. Subsequent to behavioural studies the animals were killed and rod, cone, melanopsin expression and melanopsin-expressing cells were quantified. Rod and cone loss was almost complete, melanopsin protein was reduced by 83% and melanopsin-expressing cells were reduced by 37%. Our study provides a comprehensive model of photoreceptor degeneration at the adult stage and a simple and versatile method to investigate the relation between retinal photoreceptors and the circadian system. [source] The Bmi1 polycomb gene as a target for therapies against retinal degenerationACTA OPHTHALMOLOGICA, Issue 2009Y ARSENIJEVIC Purpose In several neurodegenerative diseases the reactivation of cell cycle proteins is a key event that precedes neuronal apoptosis. We asked whether a similar phenomenon occurs in Rd1 mice, a model of retinitis pigmentosa widely used to study photoreceptor (PR) loss. Methods We used different knockout mouse models to reveal whether proteins involved in the cell cycle regulation are responsible for photoreceptor loss in the Rd1 mouse. Results At P12, an early stage of the disease, Rd1 mice displayed an increased expression of CDK4 and CDK2 among PR nuclei. PRs also undergo DNA synthesis. At P12, the polycomb protein Bmi1 was expressed in virtually all the nuclei in the inner and outer nuclear layer of both wild-type (WT) and Rd1 mice. Bmi1 promotes cell cycle progression via the repression of tumor suppressor genes. We reasoned that Bmi1 deletion could impede the aberrant CDK reactivation that characterizes neuronal apoptosis and may therefore delay retinal degeneration. We compared the histology of WT, Rd1 and Rd1;Bmi1-/- and observed the presence of 7 rows of PRs in Rd1;Bmi1-/- mice at P33, while Rd1 littermates displayed a single scattered row of PRs. ERG recordings revealed the ability of Rd1:Bmi1-/- retinas to respond to light stimuli. Both DNA synthesis and CDK4 were strongly decreased in Rd1;Bmi1-/- mice, respectively by 70% and 50% as compared to Rd1 littermates. Conclusion In conclusion, our data show for the first time a mechanism of retina degeneration involving a reactivation of the cell cycle that precedes PR death in Rd1 mice and reveal that the partial inhibition of cell cycle re-entry strongly delays PR loss. [source] Synaptic localization of neuroligin 2 in the rodent retina: Comparative study with the dystroglycan-containing complexJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2010Leona Lui Abstract Several recent studies have shown that neuroligin 2 (NL2), a component of the cell adhesion neurexins,neuroligins complex, is localized postsynaptically at hippocampal and other inhibitory synapses throughout the brain. Other studies have shown that components of the dystroglycan complex are also localized at a subset of inhibitory synapses and are coexpressed with NL2 in brain. These data prompted us to undertake a comparative study between the localization of NL2 and the dystroglycan complex in the rodent retina. First, we determined that NL2 mRNA is expressed both in the inner and in the outer nuclear layers. Second, we found that NL2 is localized both in the inner and in the outer synaptic plexiform layers. In the latter, the horseshoe-shaped pattern of NL2 and its extensive colocalization with RIM2, a component of the presynaptic active zone at ribbon synapses, argue that NL2 is localized presynaptically at photoreceptor terminals. Third, comparison of NL2 and the dystroglycan complex distribution patterns reveals that, despite their coexpression in the outer plexiform layer, they are spatially segregated within distinct domains of the photoreceptor terminals, where NL2 is selectively associated with the active zone and the dystroglycan complex is distally distributed in the lateral regions. Finally, we report that the dystroglycan deficiency in the mdx3cv mouse does not alter NL2 localization in the outer plexiform layer. These data show that the NL2- and dystroglycan-containing complexes are differentially localized in the presynaptic photoreceptor terminals and suggest that they may serve distinct functions in retina. © 2009 Wiley-Liss, Inc. [source] The distribution of neuroglobin in mouse eyeACTA OPHTHALMOLOGICA, Issue 2009Y YOU Purpose To determine the distribution of neuroglobin (Ngb) in mouse eye. Ngb is predominantly expressed in the nervous system,and at particularly high levels in the retina. Ngb may serve as a reactive oxygen scavenger and may protect the tissue of eye from ischemia/hypoxia injuries. However,the distribution of Ngb in the eye is still controversial. Methods Two polyclonal antibodies against Ngb were used in this immunohistochemical study, both of which were raised in rabbits. One of these two antibodies was generated against the whole recombinant protein of mouse Ngb and the other was generated against amino acid positions 55-70 of mouse and human Ngb. The expression of Ngb was analyzed with light microscopy on tissue sections. Results These two antibodies showed comparable results. Ngb was expressed in the layers of the retina, including the ganglion cell layer, inner and outer nuclear layers, inner and outer plexiform layers, the inner segments of the photoreceptors and the retinal pigment epithelium. Ngb was also detected in other structures of the eye, including the epithelium and endothelium of cornea,the stroma of iris,the ciliary body, the lens epithelium, and the sclera. However, Ngb was not expressed in the corneal stroma, the lens capsule, the lamellar fibers of lens, the pigment epithelium of ciliary body or the pigment layer of iris. Conclusion Ngb was found widely distributed in mouse eye. This finding can be explained by the fact that most of the structures of the eye originated from neural crest/neural ectoderm. Future experiments will focus on the distribution of Ngb at the mRNA level (in situ hybridization),and the quantitative expression levels at baseline and after hypoxic/ischemic challenge. [source] | ||||||||||