May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Regulation of Dickkopf Protein 3 in Retinal Cells and Diabetic Retina
Author Affiliations & Notes
  • Y. Sassa
    Joslin Diabetes Center/Harvard Medical School, Boston, MA
    Eye Research,
  • S.L. Rook
    Joslin Diabetes Center/Harvard Medical School, Boston, MA
    Eye Research,
  • A.C. Clermont
    Joslin Diabetes Center/Harvard Medical School, Boston, MA
    Eye Research,
  • B. Gao
    Joslin Diabetes Center/Harvard Medical School, Boston, MA
    Vascular Cell Biology,
  • E.P. Feener
    Joslin Diabetes Center/Harvard Medical School, Boston, MA
    Vascular Cell Biology,
  • L.P. Aiello
    Joslin Diabetes Center/Harvard Medical School, Boston, MA
    Eye Research, Beetham Eye Institute, Ophthalmology,
  • Footnotes
    Commercial Relationships  Y. Sassa, None; S.L. Rook, None; A.C. Clermont, None; B. Gao, None; E.P. Feener, None; L.P. Aiello, None.
  • Footnotes
    Support  EY10827
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 964. doi:
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      Y. Sassa, S.L. Rook, A.C. Clermont, B. Gao, E.P. Feener, L.P. Aiello; Regulation of Dickkopf Protein 3 in Retinal Cells and Diabetic Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):964.

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

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Abstract

Purpose: : Using proteomic analyses, we recently identified the Wnt signaling antagonist Dickkopf protein 3 (DKK3) as being reduced in the vitreous of patients with PDR. DKK–3 has tumor suppressor, apoptosis and anti–proliferative activities and is involved in cellular migration and differentiation. We examined the expression and regulation of DKK3 in retina and cultured retinal cells.

Methods: : DKK3 mRNA expression in bovine retinal capillary endothelial cells (REC), pericytes (RPC) and pigment epithelial cells (RPE) were assessed by Northern blot and RT–PCR analysis. Retinal DKK1–3 expression was evaluated in control and streptozotocin–induced diabetic mice (C57/BL6) by RT–PCR.

Results: : DKK3 gene expression was detected in all cultured retinal cells examined. Expression was 10.3– and 3.8–fold higher in RPC and RPE, respectively, than in REC. DKK3 expression was increased by cellular confluency 1.4– and 2.3–fold in REC and RPE, respectively. High glucose exposure (22mM) for 5 days decreased DKK3 gene expression in RPC 24% (p=0.039) as compared with normal glucose (5.5mM) of equal osmolarity. Insulin (100nM) increased DKK3 gene expression in RPC in a time and dose–dependent manner (180%+30% at 4 hours), an effect maintained at least 10 hours. DKK2&3, but not DKK1, were detected in normal mouse retina. DKK–3 gene expression decreased in mouse retina after 8 weeks of diabetes by 24% (p=0.017) as compared to nondiabetic retina.

Conclusions: : DKK3 expression is decreased in diabetic retina and is regulated by cell confluency, glucose concentration, and insulin in retinal cells in culture. These findings suggest a possible regulatory role of DKK3 in mediating retinal complications of diabetes.

Keywords: diabetic retinopathy • diabetes • retina 
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