May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Exploration of two key genes controlling angiogenesis in patients with increased retinal vascularization
Author Affiliations & Notes
  • M.N. Preising
    Dpt of Paediat Ophthalmology, Strabismology and Ophthalmogenetics,
    University of Regensburg, Regensburg, Germany
  • A.–L. Pina
    Clinic and Policlinic of Neurosurgery,
    University of Regensburg, Regensburg, Germany
  • H. Elflein
    Dpt of Paediat Ophthalmology, Strabismology and Ophthalmogenetics,
    University of Regensburg, Regensburg, Germany
  • R. Schmidt–Kastner
    Dept. of Neurology, University of Miami, School of Medicine, Miami, FL
  • J. Wachtlin
    Eye Dept Klinikum B. Franklin, FU Berlin, Berlin, Germany
  • U. Kellner
    Eye Dept Klinikum B. Franklin, FU Berlin, Berlin, Germany
  • B. Lorenz
    Dpt of Paediat Ophthalmology, Strabismology and Ophthalmogenetics,
    University of Regensburg, Regensburg, Germany
  • Footnotes
    Commercial Relationships  M.N. Preising, None; A. Pina, None; H. Elflein, None; R. Schmidt–Kastner, None; J. Wachtlin, None; U. Kellner, None; B. Lorenz, None.
  • Footnotes
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Investigative Ophthalmology & Visual Science May 2004, Vol.45, 4044. doi:
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      M.N. Preising, A.–L. Pina, H. Elflein, R. Schmidt–Kastner, J. Wachtlin, U. Kellner, B. Lorenz; Exploration of two key genes controlling angiogenesis in patients with increased retinal vascularization . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4044.

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

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Abstract

Abstract: : Purpose: Retinopathy of Prematurity (ROP), Age–related Macular Degeneration (AMD), vasoproliferative retinal tumors, and Exudative Vitreoretinopathies (FEVR and EVR1) are characterized by increased neovascularization. In ROP neovascularization was attributed to hypoxia occurring after oxygen supplementation, and ischemia due to deposits on Bruch’s membrane was discussed in AMD. Neovascularization in FEVR and EVR1 phenotypically resembles ROP. Finally, vascularisation in retinal tumors occurs due to the need for oxygen and nutrient supplementation in the fast growing tissue. HIF1A is the central component of a sensor mechanism for hypoxia and the coordinating transcriptional regulator for hypoxia–related gene expression, including the angiogenesis regulator VEGF. By contrast, PEDF is a major anti–angiogenic factor. PEDF and HIF1A have not been tested in retinal neovascularization disorders before. This study has explored the participation of mutations in PEDF and HIF1A in disorders characterized by retinal neovascularization. Methods: Thirteen patients with neovascularization disorders (4 with ROP of various stages, 3 with AMD, 2 with vasoproliferative retinal tumors, 4 with vitreoretinopathies) were screened for mutations in PEDF and HIF1A by PCR–SSCP and direct sequencing. Results: Several polymorphisms were identified in PEDF. The most frequent (M72T) was identified in 7/13 probands. A missense mutation was identified in HIF1A in all ROP cases screened, in 2/3 AMD cases, and in both probands of a twin pair with a vasoproliferative retinal tumor, but not in FEVR and EVR1. The mutation could be found in 8/90 control alleles (2 homozygous probands). Conclusions: The M72T mutation in PEDF was very frequent in our set of samples. Therefore, we agree with previous reports that M72T is not a disease causing allele. The mutation in HIF1A was unexpectedly frequent in ROP, AMD, and vasoproliferative retinal tumors while infrequent in the general population. Recently increased activity has been attributed to its gene product, suggesting overshooting angiogenesis responses. The aim of this explorative study was to identify disorders for which an extended screen of HIF1A or PEDF is reasonable. Our results urge us to extend the screening of ROP and AMD cases and to confirm the data in a larger subset of patients.

Keywords: neovascularization • hypoxia • genetics 
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