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Jared Watters, Saptarshi Biswas, Galina Bachay, Dale Donald Hunter, William J Brunken; The Role of Laminin β2 in Retinal Vascular Basement Membrane Organization. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5401.
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© ARVO (1962-2015); The Authors (2016-present)
The vascular basement membrane (BM) regulates vascular maturation, permeability, and stability. Changes in its composition occur with aging and accompanying pathologies. Laminins, heterotrimeric glycoproteins, are important molecules that regulation BM formation and organization. We examined whether the disruption of Lamb2 alters the expression of retinal vascular BM proteins.
Littermate Lamb2-/- and WT retinae were dissected and flat-mounted at P20. These retinae were stained for the BM proteins found in the retinal vasculature (N=3 for all stains) and imaged. Chain-specific antibodies were used for the laminin stains. The fluorescence was compared between mutant and WT littermates by calculating the relative fluorescence intensity (RFI): mutant MFI/WT MFI = RFI; statistical significance was measured by two-tailed Student's T-test.
The expression of laminin α2 was significantly decreased in Lamb2-/- veins (p=0.011) and arteries (p=0.007). The expression of laminin α5 was significantly decreased in Lamb2-/- veins (p=0.005), arteries (p=0.004), the intermediate vascular plexus (IVP) (p=0.011), and the deep vascular plexus (DVP) (p=0.014). The expression of laminin γ3 was significantly decreased in Lamb2-/- veins (p=0.001), the IVP (p=0.013), and the DVP (p=0.012). The expression of laminin α4, laminin β1, fibronectin, and collagen IV was unaffected in all vessels. The expression of perlecan was significantly increased in Lamb2-/- arteries (p=0.005), while the expression of agrin was significantly increased in the veins (p=0.048). The permeability of these vessels is being studied.
These results demonstrate that the retinal vascular BM is dynamic and the disruption of a single organizing component leads to changes in the expression of various BM molecules. The work also demonstrates that vascular ECM is differentially spatially regulated i.e., veins, arteries, and capillaries. This dynamic spatial regulation supports the different functions of these compartments and may explain why attempts to control retinal neovascularization therapeutically have remained elusive.
This is a 2020 ARVO Annual Meeting abstract.
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