Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease

Joachim Spranger, Martin Osterhoff, Manja Reimann, Matthias Möhlig, Michael Ristow, Mary Kay Francis, Vincent Cristofalo, Hans Peter Hammes, Gillian Smith, Michael Boulton, Andreas F H Pfeiffer

Research output: Contribution to journalArticle

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Abstract

Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR). Pigment epithelium-derived factor (PEDF) has been shown to be a major antiangiogenic growth factor in the mammalian eye. PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease. However, whether this concept of a reduced angiogenesis inhibitor holds true in humans is as yet unclear. In this study, we analyzed the in vivo regulation of PEDF in patients with and without hypoxic eye disease. We used immunoblots to measure PEDF in ocular fluids obtained from 64 nondiabetic and diabetic patients. In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy. The PEDF concentrations in patients with PDR (P <0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P <0.001) were lower than in control patients. Levels of PEDF were replenished in PDR patients with previous retinal scatter photocoagulation compared with PDR patients without previous photocoagulation (P = 0.01). Immunohistochemistry revealed an interstitial staining pattern as expected for a secreted protein, with an intense staining in retinas of patients without proliferative eye disease. However, in patients with PDR, little or no staining was detectable. Our data strongly support the concept that retinal angiogenesis is induced by loss of the major angiogenesis inhibitor in the eye, PEDF, in combination with an increased expression of angiogenic growth factors such as vascular endothelial growth factor. Our findings suggest that substitution of angiogenesis inhibitors may be an effective approach in the treatment of PDR.

Original languageEnglish (US)
Pages (from-to)2641-2645
Number of pages5
JournalDiabetes
Volume50
Issue number12
StatePublished - Dec 2001
Externally publishedYes

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Eye Diseases
Diabetic Retinopathy
Retinal Neovascularization
Angiogenesis Inhibitors
Retina
Light Coagulation
Staining and Labeling
Intercellular Signaling Peptides and Proteins
Immunohistochemistry
pigment epithelium-derived factor
Retinal Vein Occlusion
Angiogenesis Inducing Agents
Vascular Endothelial Growth Factor A
Animal Models

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Spranger, J., Osterhoff, M., Reimann, M., Möhlig, M., Ristow, M., Francis, M. K., ... Pfeiffer, A. F. H. (2001). Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes, 50(12), 2641-2645.

Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. / Spranger, Joachim; Osterhoff, Martin; Reimann, Manja; Möhlig, Matthias; Ristow, Michael; Francis, Mary Kay; Cristofalo, Vincent; Hammes, Hans Peter; Smith, Gillian; Boulton, Michael; Pfeiffer, Andreas F H.

In: Diabetes, Vol. 50, No. 12, 12.2001, p. 2641-2645.

Research output: Contribution to journalArticle

Spranger, J, Osterhoff, M, Reimann, M, Möhlig, M, Ristow, M, Francis, MK, Cristofalo, V, Hammes, HP, Smith, G, Boulton, M & Pfeiffer, AFH 2001, 'Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease', Diabetes, vol. 50, no. 12, pp. 2641-2645.
Spranger J, Osterhoff M, Reimann M, Möhlig M, Ristow M, Francis MK et al. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes. 2001 Dec;50(12):2641-2645.
Spranger, Joachim ; Osterhoff, Martin ; Reimann, Manja ; Möhlig, Matthias ; Ristow, Michael ; Francis, Mary Kay ; Cristofalo, Vincent ; Hammes, Hans Peter ; Smith, Gillian ; Boulton, Michael ; Pfeiffer, Andreas F H. / Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. In: Diabetes. 2001 ; Vol. 50, No. 12. pp. 2641-2645.
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