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Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance.

ABSTRACT: BACKGROUND:Myopia (short-sightedness) affects approximately 1.4 billion people worldwide, and prevalence is increasing. Animal models induced by defocusing lenses show striking similarity with human myopia in terms of morphology and the implicated genetic pathways. Less is known about proteome changes in animals. Thus, the present study aimed to improve understanding of protein pathway responses to lens defocus, with an emphasis on relating expression changes to no lens control development and identifying bidirectional and/or distinct pathways across myopia and hyperopia (long-sightedness) models. RESULTS:Quantitative label-free proteomics and gene set enrichment analysis (GSEA) were used to examine protein pathway expression in the retina/RPE of chicks following 6 h and 48 h of myopia induction with -?10 dioptre (D) lenses, hyperopia induction with +10D lenses, or normal no lens rearing. Seventy-one pathways linked to cell development and neuronal maturation were differentially enriched between 6 and 48 h in no lens chicks. The majority of these normal developmental changes were disrupted by lens-wear (47 of 71 pathways), however, only 11 pathways displayed distinct expression profiles across the lens conditions. Most notably, negative lens-wear induced up-regulation of proteins involved in ATP-driven ion transport, calcium homeostasis, and GABA signalling between 6 and 48 h, while the same proteins were down-regulated over time in normally developing chicks. Glutamate and bicarbonate/chloride transporters were also down-regulated over time in normally developing chicks, and positive lens-wear inhibited this down-regulation. CONCLUSIONS:The chick retina/RPE proteome undergoes extensive pathway expression shifts during normal development. Most of these pathways are further disrupted by lens-wear. The identified expression patterns suggest close interactions between neurotransmission (as exemplified by increased GABA receptor and synaptic protein expression), cellular ion homeostasis, and associated energy resources during myopia induction. We have also provided novel evidence for changes to SLC-mediated transmembrane transport during hyperopia induction, with potential implications for signalling at the photoreceptor-bipolar synapse. These findings reflect a key role for perturbed neurotransmission and ionic homeostasis in optically-induced refractive errors, and are predicted by our Retinal Ion Driven Efflux (RIDE) model.

SUBMITTER: Riddell N

PROVIDER: S-EPMC6116556 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance.

Riddell Nina N Faou Pierre P Crewther Sheila G SG

BMC developmental biology 20180829 1

<h4>Background</h4>Myopia (short-sightedness) affects approximately 1.4 billion people worldwide, and prevalence is increasing. Animal models induced by defocusing lenses show striking similarity with human myopia in terms of morphology and the implicated genetic pathways. Less is known about proteome changes in animals. Thus, the present study aimed to improve understanding of protein pathway responses to lens defocus, with an emphasis on relating expression changes to no lens control developme ...[more]

PMID: 30157773

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Project description:PurposeWe evaluated the repeatability of wide-field en face swept-source optical coherence tomography angiography (SS-OCTA) in healthy subjects.MethodsHealthy subjects underwent two imaging sessions, on average 8 days apart, with a 100 kHz SS-OCTA instrument. The imaging protocol included a central 3 × 3 and 12 × 12 mm scans of the four quadrants resulting in more than a 70° wide-field OCTA of the posterior pole. Quantitative analysis was performed using the inbuilt Macular Density Algorithm Version v0.6.1 and AngioTool software. Consistency for the foveal avascular zone (FAZ), vessel density, and perfusion density of the superficial and deep capillary plexus slabs and the wide-field OCTA superficial slab, and the number of artefacts on the wide-field images were assessed.ResultsA total of 21 healthy volunteers (seven men and 14 women; mean age 32 years; range, 18-61; standard deviation, 10.28 years) were included in this analysis. Internal consistency was highest for FAZ area with an intraclass correlation (ICC) = 0.998 (95% confidence interval [CI], 0.997-0.999), a FAZ perimeter with an ICC = 0.995 (95% CI, 0.990-0.997), a FAZ circularity with an ICC= 0.976 (95% CI, 0.956-0.987), followed by the vessel density of the inner ring in the superficial slab with an ICC = 0.834 (95% CI, 0.691-0.911), and a vessel density of the inner ring in the deep slab with an ICC = 0.523 (95% CI, 0.113-0.744).The reproducibility of the average vessels length of the wide-field OCTA cropped images was strong (ICC = 0.801; 95% CI, 0.624-0.895), followed by the reproducibility of total number of junctions (ICC = 0.795; 95% CI, 0.613-0.892) and the vessels percentage area (ICC = 0.662; 95% CI, 0.361-0.821).ConclusionsThe level of reproducibility for assessing the microvascular anatomy in wide-field OCTA is strong and can be used to quantify microvascular changes over time. Refinements in analysis strategies and a consensus of which parameters are most useful for quantitative assessment of wide-field OCTA images would be useful in the future.Translational relevanceThese findings bridge the gap between basic imaging research and clinical use for quantitative wide-field OCTA.

Project description:This study investigated the effects of imposed optical defocus on the expression patterns of bone morphogenetic protein 4 and 7 (BMP4, BMP7) in chick retinal pigment epithelium (RPE), as indicators of roles in postnatal eye growth regulation. BMP4 and BMP7 gene and protein expression patterns were characterized for retina, RPE and choroid tissues of young normal White-Leghorn chickens. The effects of short-term (2 and 48 h) exposure to monocular +10 and -10 diopter (D) lenses on RPE gene expression of BMP4 and BMP7 were also examined. Tissues from both treated and fellow eyes as well as from eyes of age-matched untreated birds were included in the latter experiment. Of ocular tissues comprising the posterior wall of the chick eye, RPE showed the highest expression of BMP4 and BMP7 mRNA, compared to retina and choroid. Western blots and immunohistochemistry confirmed the expression of BMP4 and BMP7 protein in all layers - retina, RPE, choroid and sclera. With imposed defocus, both BMP4 and BMP7 showed bidirectional changes in expression in RPE, however, with different temporal patterns. With +10 D lenses, BMP4 gene expression was up-regulated after both 2 and 48 h of treatment, while BMP7 expression was up-regulated only after 48 h of lens wear. With -10 D lenses, both BMP4 and BMP7 showed down-regulation of gene expression for both 2 and 48 h treatment durations. With the -10 D lens treatment applied for 48 h, gene expression for both BMP4 and BMP7 was also down-regulated in contralateral fellows of treated eyes compared to eyes of untreated chicks. The rapid changes in gene expression in chick RPE observed for both BMP4 and BMP7, up or down according to the sign of imposed optical defocus, resemble similar trends reported for BMP2. Further studies are needed to confirm the roles of BMPs as ocular growth modulators, as suggested by these data. The data also suggest a role for the RPE as a conduit for relaying growth modulatory retinal signals.

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Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance.

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Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance.

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