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      A microarray analysis of retinal transcripts that are controlled by image contrast in mice

      research-article
      , ,
      Molecular Vision
      Molecular Vision

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          Abstract

          Purpose

          The development of myopia is controlled by still largely unknown retinal signals. The aim of this study was to investigate the changes in retinal mRNA expression after different periods of visual deprivation in mice, while controlling for retinal illuminance.

          Methods

          Each group consisted of three male C57BL/6 mice. Treatment periods were 30 min, 4 h, and 6+6 h. High spatial frequencies were filtered from the retinal image by frosted diffusers over one eye while the fellow eyes were covered by clear neutral density (ND) filters that exhibited similar light attenuating properties (0.1 log units) as the diffusers. For the final 30 min of the respective treatment period mice were individually placed in a clear Perspex cylinder that was positioned in the center of a rotating (60 degrees) large drum. The inside of the drum was covered with a 0.1 cyc/degree vertical square wave grating. This visual environment was chosen to standardize illuminances and contrasts seen by the mice. Labeled cRNA was prepared and hybridized to Affymetrix GeneChip® Mouse Genome 430 2.0 arrays. Alterations in mRNA expression levels of candidate genes with potential biological relevance were confirmed by semi-quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).

          Results

          In all groups, Egr-1 mRNA expression was reduced in diffuser-treated eyes. Furthermore, the degradation of the spatial frequency spectrum also changed the cFos mRNA level, with reduced expression after 4 h of diffuser treatment. Other interesting candidates were Akt2, which was up-regulated after 30 min of deprivation and Mapk8ip3, a neuron specific JNK binding and scaffolding protein that was temporally regulated in the diffuser-treated eyes only.

          Conclusions

          The microarray analysis demonstrated a pattern of differential transcriptional changes, even though differences in the retinal images were restricted to spatial features. The candidate genes may provide further insight into the biochemical short-term changes following retinal image degradation in mice. Because deprivation of spatial vision leads to increased eye growth and myopia in both animals and humans, it is believed some of the identified genes play a role in myopia development.

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          Most cited references61

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          Cellular survival: a play in three Akts.

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            The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase.

            The serine/threonine protein kinase encoded by the Akt proto-oncogene is catalytically inactive in serum-starved primary and immortalized fibroblasts. Here we show that Akt and the Akt-related kinase AKT2 are activated by PDGF. The activation was rapid and specific, and it was abrogated by mutations in the Akt Pleckstrin homology (PH) domain. The Akt activation was also shown to depend on PDGFR beta tyrosines Y740 and Y751, which bind phosphatidylinositol 3-kinase (PI 3-kinase) upon phosphorylation. Moreover, Akt activation was blocked by the PI 3-kinase-specific inhibitor wortmannin and the dominant inhibitory N17Ras. Conversely, Akt activity was induced following the addition of phosphatidylinositol-3-phosphate to Akt immunoprecipitates from serum-starved cells in vitro. These results identify Akt as a novel target of PI 3-kinase and suggest that the Akt PH domain may be a mediator of PI 3-kinase signaling.
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              Homeostasis of eye growth and the question of myopia.

              As with other organs, the eye's growth is regulated by homeostatic control mechanisms. Unlike other organs, the eye relies on vision as a principal input to guide growth. In this review, we consider several implications of this visual guidance. First, we compare the regulation of eye growth to that of other organs. Second, we ask how the visual system derives signals that distinguish the blur of an eye too large from one too small. Third, we ask what cascade of chemical signals constitutes this growth control system. Finally, if the match between the length and optics of the eye is under homeostatic control, why do children so commonly develop myopia, and why does the myopia not limit itself? Long-neglected studies may provide an answer to this last question.
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                Author and article information

                Journal
                Mol Vis
                MV
                Molecular Vision
                Molecular Vision
                1090-0535
                2007
                18 June 2007
                : 13
                : 920-932
                Affiliations
                [1]Section for Neurobiology of the Eye, University Eye Hospital Tuebingen, Tuebingen, Germany
                Author notes
                Correspondence to: Marita Pauline Feldkaemper, Section for Neurobiology of the Eye, University Eye Hospital Tuebingen, Calwerstr. 7/1, 72076 Tuebingen, Germany; Phone: (+49) 7071/29-87424; FAX: (+49) 7071/29-5196; email: marita.feldkaemper@ 123456uni-tuebingen.de
                Article
                a98
                2774458
                17653032
                cb86380a-558c-454a-8746-90f208c0061a
                Copyright @ 2007

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 January 2007
                : 30 May 2007
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                Research Article
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                Vision sciences
                Vision sciences

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