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D. A. Karagiannis, I. Semkova, Y. Liang, N. Kociok, M. Paulsson, A. M. Joussen; Characterization of Experimental Choroidal Neovascularization in Wildtype Mice Over Different Timepoints. Invest. Ophthalmol. Vis. Sci. 2009;50(13):788. doi: https://doi.org/.
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The main cause of severe vision loss in patients with age-related macular degeneration (AMD) is choroidal neovascularization (CNV). Basement membranes (BM) are key components of vascular walls, inner limiting membrane, Bruch's membrane, etc. In vitro has been shown that changes in BM proteins play an important role in angiogenesis. We investigated different BM proteins nidogen-1, nidogen-2, laminins (γ1 and γ3 chain), collagen type-IV and perlecan, their expression and the structure of CNV lesions over a course of time.
An experimental animal model of AMD was used to investigate the role of BM proteins. Laser photocoagulation was performed to induce rupture of Bruch’s membrane and subsequent neovascular growth in C57Bl/6J (WT) animals. We determined 4 different time points to investigate the changes 24 hours, 1 week, 2 weeks and 4 weeks after laser procedure.The choroid was flatmounted and labeled with Isolectin IB-4.Distribution and expression of the studied proteins in choroid and retina were investigated by immunohistochemistry on paraffin sections. CNV lesions were investigated by fluorescein angiograms in vivo, respectively.
The proteins were located in different BMs. Nidogens, perlecan and laminin were expressed in vascular walls but not in Bruch’s membrane. Collagen4 was expressed in vascular walls, inner limiting membrane and Bruch’s membrane.Immunohistochemistry showed the expression of all studied proteins in CNV lesions but at different timepoints. Nidogen-1 showed its highest expression 2 weeks after laser. Nidogen-2 was expressed until the 2nd timepoint. Fluorescein angiograms showed a peak of pathological vascular leakage at the 2nd timepoint. Flatmount preparation showed the same lesion sizes 24 hours and 2 weeks after laser. 1 week after laser the lesions size decreased. 4 weeks after laser the lesions were confluent.
The distribution of the analyzed proteins varied extensively demonstrating a different assembly of ocular BMs. The investigated proteins were all expressed in CNV lesions, suggesting that CNV lesions change the composition of BMs by inducing BM-protein expression.The flatmounts and the fluorescein angiograms showed that CNV lesions underwent changes in size and formation, suggesting a mechanism of tissue remodeling similar to healing processes in other tissues. Further studies are needed to determine the role of BMs in laser-induced CNV.
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