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H. Meng, W. Wang, G. Jiang, B. Uyesugi, W. Hu, S. Huang, H. Gao, X. Qiao; Src Family Kinase Expressions In The Retina Of Vldlr Knockout Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4155.
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© ARVO (1962-2015); The Authors (2016-present)
Src family kinases (SFKs) are membrane–attached non–receptor protein tyrosine kinases that link a variety of extracellular cues to intracellular signal pathways. Recent finding indicates that SFKs are capable of interacting with the receptors of several major angiogenic factors and are involved in pathological angiogenesis. In the present study, we investigate the SFK expression profile and its potential roles in the retina of wildtype and vldlr knockout mice (vldlr–/–) with subretinal neovascularization.
A commercially available RT–PCR profiling kit for SFKs was used to determine how many members of SFK family were expressed in the retina. Western blot and immunohistochemistry were utilized to examine the levels of SFK protein and cellular origin. The responses of SFKs and several angiogenic factors to in vitro stimulation of retinal tissues with a cocktail containing inflammatory reagents and hydrogen peroxide were evaluated. The levels of angiogenic factor mRNA expression were measured by RT–PCR.
Preliminary study revealed that eight of the eleven SFK members, namely Fyn, Hck, Lck, Lyn, Ptk2, Ptk2b, Yes, and Src, were expressed in the adult mouse retina. Compared to wildtype mice, the Lck mRNA expression was upregulated in the retina of vldlr–/– mice, but no obvious changes were found in the expression of other SFKs. Western blot analysis confirmed that the expression of Yes protein level was normal in the retina of vldlr–/– mice. Src immunoreactivity was mainly localized in the retinal ganglion cell layer, inner nuclear layer and inner segment of photoreceptors, and there was no significant difference in Src retinal localization between the two genotypes. Except Lck mRNA which was increased, most of SFK mRNAs were downregulated in response to the inflammatory cocktail stimulation in the wildtype retina. The levels of angiogenic factor VEGF–A and bFGF were sensitive to inflammatory stimulation with a tendency to decrease in wildtype. However, bFGF mRNA expression was increased in response to inflammatory stimulation in the retina of vldlr–/– mice.
Taken together, the majorities of SFK members are expressed in the retina and are sensitive to the inflammatory stimulation. These data suggest that SFKs might be involved in the pathologic subretinal neovascularization in vldlr–/– mice.
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