Dataset Information

Expression and distribution of peroxiredoxins in the retina and optic nerve.

ABSTRACT: Oxidative stress is implicated in various pathological conditions of the retina and optic nerve. Peroxiredoxins (Prdxs) comprise a recently characterized family of antioxidant enzymes. To date, little information exists regarding the distribution of Prdxs in the eye. Herein, we employed a combination of qRT-PCR, immunohistochemistry and Western blotting to determine the level of expression and distribution of the six Prdx isoforms in the retina and optic nerve of the rat. In addition, we performed some parallel analyses on the common marmoset (Callithrix Jacchus). In the rat, all of the Prdx transcripts were expressed in relatively high amounts in both retina and optic nerve, with abundances ranging from approximately 3-50 % of the level of the housekeeping gene cyclophilin. With regard to protein expression, each isoform was detected in the retina and optic nerve by either Western blotting and/or immunohistochemistry. Excepting Prdx4, there was a good correspondence between the rodent and primate results. In the retina, Prdx1 and Prdx2 were principally localized to neurons in the inner nuclear layer and cone photoreceptors, Prdx3 and Prdx5 displayed characteristic mitochondrial immunolabeling, while Prdx6 was associated with astrocytes and Müller cells. In the optic nerve, Prdx1 was robustly expressed by oligodendrocytes, Prdx3 and Prdx5 were observed in axons, and Prdx6 was restricted to astrocytes. The present findings augment our understanding of the distribution and expression of the Prdxs in the retina and optic nerve of rodents and primates and lay the foundation for subsequent analysis of their involvement in relevant blinding diseases.

SUBMITTER: Chidlow G

PROVIDER: S-EPMC5065902 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Expression and distribution of peroxiredoxins in the retina and optic nerve.

Chidlow Glyn G Wood John P M JP Knoops Bernard B Casson Robert J RJ

Brain structure & function 20151026 8

Oxidative stress is implicated in various pathological conditions of the retina and optic nerve. Peroxiredoxins (Prdxs) comprise a recently characterized family of antioxidant enzymes. To date, little information exists regarding the distribution of Prdxs in the eye. Herein, we employed a combination of qRT-PCR, immunohistochemistry and Western blotting to determine the level of expression and distribution of the six Prdx isoforms in the retina and optic nerve of the rat. In addition, we perform ...[more]

PMID: 26501408

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Project description:PurposeTo investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT).DesignProspective, cross-sectional, observational study.SubjectsA total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls.MethodsHigh-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 μm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 μm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula.Main outcome measuresHorizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls.ResultsPatients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%.ConclusionsOur study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis.

Project description:Central nervous system (CNS) trauma and neurodegenerative disorders trigger a cascade of cellular and molecular events resulting in neuronal apoptosis and regenerative failure. The pathogenic mechanisms and gene expression changes associated with these detrimental events can be effectively studied using a rodent optic nerve crush (ONC) model. The purpose of this study was to use a mouse ONC model to: (a) evaluate changes in retina and optic nerve (ON) gene expression, (b) identify neurodegenerative pathogenic pathways and (c) discover potential new therapeutic targets.Only 54% of total neurons survived in the ganglion cell layer (GCL) 28 days post crush. Using Bayesian Estimation of Temporal Regulation (BETR) gene expression analysis, we identified significantly altered expression of 1,723 and 2,110 genes in the retina and ON, respectively. Meta-analysis of altered gene expression (?1.5, ?-1.5, p?<?0.05) using Partek and DAVID demonstrated 28 up and 20 down-regulated retinal gene clusters and 57 up and 41 down-regulated optic nerve clusters. Regulated gene clusters included regenerative change, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. Expression of selected genes (Vsnl1, Syt1, Synpr and Nrn1) from retinal and ON neuronal clusters were quantitatively and qualitatively examined for their relation to axonal neurodegeneration by immunohistochemistry and qRT-PCR.A number of detrimental gene expression changes occur that contribute to trauma-induced neurodegeneration after injury to ON axons. Nrn1 (synaptic plasticity gene), Synpr and Syt1 (synaptic vesicle fusion genes), and Vsnl1 (neuron differentiation associated gene) were a few of the potentially unique genes identified that were down-regulated spatially and temporally in our rodent ONC model. Bioinformatic meta-analysis identified significant tissue-specific and time-dependent gene clusters associated with regenerative changes, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. These ONC induced neuronal loss and regenerative failure associated clusters can be extrapolated to changes occurring in other forms of CNS trauma or in clinical neurodegenerative pathological settings. In conclusion, this study identified potential therapeutic targets to address two key mechanisms of CNS trauma and neurodegeneration: neuronal loss and regenerative failure.

Dataset Information

Expression and distribution of peroxiredoxins in the retina and optic nerve.

Publications

Expression and distribution of peroxiredoxins in the retina and optic nerve.

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