May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Experimental Choroidal Neovascularization Induced in Nidogen-1 and Nidogen-2 Mutant Mice
Author Affiliations & Notes
  • I. Semkova
    Ophthalmology, University of Duesseldorf, Duesseldorf, Germany
  • M. Huemmeke
    Ophthalmology,
    University of Cologne, Cologne, Germany
  • M. S. P. Ho
    Biochemistry,
    University of Cologne, Cologne, Germany
  • N. Kociok
    Ophthalmology, University of Duesseldorf, Duesseldorf, Germany
  • M. Paulsson
    Biochemistry,
    University of Cologne, Cologne, Germany
  • A. M. Joussen
    Ophthalmology, University of Duesseldorf, Duesseldorf, Germany
  • Footnotes
    Commercial Relationships  I. Semkova, None; M. Huemmeke, None; M.S.P. Ho, None; N. Kociok, None; M. Paulsson, None; A.M. Joussen, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3429. doi:https://doi.org/
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    • Get Citation

      I. Semkova, M. Huemmeke, M. S. P. Ho, N. Kociok, M. Paulsson, A. M. Joussen; Experimental Choroidal Neovascularization Induced in Nidogen-1 and Nidogen-2 Mutant Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3429. doi: https://doi.org/.

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

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Abstract

Purpose: : Bruch’s membrane becomes abnormal in several disease including age-related macular degeneration (AMD). Nidogens (-1;-2) are key components of all basement membranes (BMs) that form BM assembly connecting the laminins (gamma1 chain) and type IV collagen and integrating other BM components (perlecan). In vitro has been shown that laminin-nidogen complex plays an important modulatory role in angiogenesis. The expression and distribution of nidogens in ocular BM as well as their role in angiogenesis in vivo have not been investigated.

Methods: : Laser photocoagulation-induced rupture of the Bruch’s membrane in nidogen-1 gene knockout , nidogen-2 -deficient mice as well as C57Bl/6J (WT) mice was used as an experimental model of AMD. Choroidal neovascular (CNV) lesions were investigated on choroidal flat-preparations after CD31 labeling and after perfusion with rhodamine-conjugated concanavalin-A and also on paraffin sections. Distribution and expression of nidogens, laminin gamma1, collagen-IV and perlecan in Bruch’s membrane, choroid and retina were investigated by immunochemistry on paraffin sections.

Results: : Nidogen-1 and nidogen-2 proteins were not expressed in the ocular BMs of nidogen-1 and nidogen-2 mutant mice respectively. Laminin-gamma1, collagen-IV and perlecan were located to the Bruch’s membrane and other BMs including vascular walls and no differences in their expression was observed between nidogen mutant and WT mice. Without damage, we did not observe abnormal angiogenic alterations in retina/choroid region of nidogen mutant mice. The both mutant mice lines showed no morphological abnormalities and their BM structures including Bruch’s membrane appeared normal. After laser injury, pathological vascular leakage and CNV lesions in nidogen mutant mice were similar to those seen in WT mice.

Conclusions: : Under normal conditions, in ndogen-1-/- and nidogen-2-/- mice we detected morphologically normal ocular BMs, normal angiogenesis and there were no evident alterations in the cellular architecture due to absence of nidogen-1 or nidogen-2 respectively. The absence of nidogen-1 and nidogen-2 respectively did not influence the development of CNV after laser photocoagulation. Previously was suggested that the loss of nidogen-1 respectively nidogen-2 function may be compensated by the natural presence and/or de novo up-regulation of nidogen-2 or nidogen-1 respectively. However, the exact structural and/or functional role of nidogens remains to be determined.

Keywords: age-related macular degeneration • choroid: neovascularization • extracellular matrix 
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