April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Difference in Gene Expression between the Macula and the Peripheral Retina: Genome-wide Study on Monkey
Author Affiliations & Notes
  • MARILYN DERNIGOGHOSSIAN
    centre de recherche des cordeliers, Paris, France
    UNIVERSITE PARIS 5 PARIS 6, PARIS, France
  • Pierre Raphael Rothschild
    centre de recherche des cordeliers, Paris, France
    AP-HP, Groupe Hospitalier Cochin-Hôtel-Dieu, Service d, PARIS, France
  • Sawsen Salah
    centre de recherche des cordeliers, Paris, France
  • Maria Paz
    Mathomics, Center for Mathematical Modeling & Center for Genome Regulation, University of Chile, Santiago, Chile., SANTIAGO, Chile
  • Wilfred Van Ijken
    Department of Biochemistry and Centre for Biomedical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., ROTTERDAM, Netherlands
  • Alejandro Maass
    Mathomics, Center for Mathematical Modeling & Center for Genome Regulation, University of Chile, Santiago, Chile., SANTIAGO, Chile
  • Patricia Lassiaz
    centre de recherche des cordeliers, Paris, France
  • Francine F Behar-Cohen
    centre de recherche des cordeliers, Paris, France
    UNIVERSITE DE LAUSANNE, Jules-Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland., LAUSANNE, Switzerland
  • Charlotte Andrieu-Soler
    centre de recherche des cordeliers, Paris, France
    UNIVERSITE PARIS 5 PARIS 6, PARIS, France
  • Footnotes
    Commercial Relationships MARILYN DERNIGOGHOSSIAN, None; Pierre Raphael Rothschild, None; Sawsen Salah, None; Maria Paz, None; Wilfred Van Ijken, None; Alejandro Maass, None; Patricia Lassiaz, None; Francine Behar-Cohen, None; Charlotte Andrieu-Soler, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4991. doi:
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      MARILYN DERNIGOGHOSSIAN, Pierre Raphael Rothschild, Sawsen Salah, Maria Paz, Wilfred Van Ijken, Alejandro Maass, Patricia Lassiaz, Francine F Behar-Cohen, Charlotte Andrieu-Soler, ; Difference in Gene Expression between the Macula and the Peripheral Retina: Genome-wide Study on Monkey. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4991.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The macula represents less than 4% of the retina but is responsible of virtually most of our vision. In many diseases, the macula is the major part of the retina that will be affected and that will degenerate. We were interested in identifying the molecular differences between the macula and the peripheral retina in order to understand why the macular region is more sensitive to diseases.

Methods: The retinas of a monkey were kept for analysis. Punchs of the peripheral neuroretina (n=3) or macula (n=2) were isolated. RNA was extracted and quantified by RNA-Sequencing (High-seq, Illumina). Genes expressions of the periphery were compared to the macula. Selected genes (q-value < 0.05, RPKM >= 1 and Fold Change >=1.3) were used for pathways enrichment analysis.

Results: The whole transcriptome was analysed. More than 30,000 genes were studied. 4360 genes were found to be deferentially expressed in the macula vs the periphery. Several interleukin gene pathways with deferentially expressed genes were found to be enriched in the macula, such as the IL-2, IL-5, IL-6 and IL-7 pathways. The TGF, insulin, glycogen metabolism, glycolysis, gluconeogenesis and cholesterol biosynthesis signaling pathways were also deferentially expressed in the macula vs the periphery. Finally several genes involved in the potassium and sodium channels function were different in the macula (Potassium: KCNIP3 is under-expressed, KCTD14 is over-expressed; Sodium: SCN3B is under-expressed, SCN8A is over-expressed).

Conclusions: We have shown that the macula deferentially expresses genes involved in insulin, glycolysis and gluconeogenesis pathways.This is interesting because in macula of patients with Macular telangectasia type 2, 10 enzymes involved in the glycolytic pathways decrease in abundance . We have also shown that several pathways involved in the immune system are deferentially expressed (Interleukins, TGF). IL-6 has been shown to be over-expressed in the vitreous of patients with Diabetic Macular Edema. Furthermore, the cholesterol and the apo proteins have an important role in Age-Related Macular Degeneration. The fact that the cholesterol biosynthesis is different between the macula and the periphery is particularly interesting. Finally, the fact that several sodium and potassium channels are deferentially expressed in the macula could explain part of the edema found in the macula of diabetic patients.

Keywords: 688 retina • 537 gene screening • 585 macula/fovea  
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