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Norbert Kociok, Yong Liang, Sabrina V. Klein, Antonia M. Joussen; The mRNA Expression of Netrin 4 and of Netrin Receptors in an OIR Mouse Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4835.
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The pathological proliferation of vessels in the retina has a dramatic effect on the visus. Recently it has been found that Netrins, a family of laminin-related extracellular matrix binding secreted molecules are involved in a variety of developmental events including adhesion in the nervous system as well as neoangiogenesis. Netrin 4 promotes neurite extension and may be involved in vasculogenesis. Neogenin, DCC (deleted in colorectal carcinoma), and UNC5A-D (uncoordinated) are known as netrin receptors.
In a OIR mouse model the mRNA levels for VEGF, Netrin 4, DCC, neogenin, UNC5A-D, and the calibration genes CANX, RPL13A, and SDHA in the mouse retinas after oxygenation were compared to retinas of mice kept in normal room oxygenation by Real Time RT-PCR using SYBR Green I (Molecular Probes, Eugene, OR) on an iCycler (Bio-Rad Laboratories, Hercules, CA.).
Netrin 4, and the receptors neogenin, DCC, UNC5A-D are expressed both in the normal as well as the hypoxic mouse retina. To quantify the retina mRNA expression at P14, P17 and P21 we performed a Real Time-RT-PCR analysis. The mRNA expression of these genes as well as VEGF was normalized to their level at normoxic conditions (=1). The most significant alterations at P17 are presented: The normalized expression of VEGF has dropped to 0.05± 0.08 when compared to the untreated controls. The normalized mRNA expression at P17 of Netrin 4, Neogenin and DCC have also dropped to 0.06± 0.07, 0.03±0.03, and 0.09±0.13, respectively. Whereas the expression of the receptors UNC5D and UNC5C also clearly dropped at P17 to 0.11±0.007 and 0.05±0.02, the expression of UNC5B remained constant at 0.76±0.11. The mRNA expression of UNC5A declined to 0.48±0.12.
Under relative hypoxic conditions the mRNA expression of Netrin 4 and of the known receptors of netrins changed dramatically suggesting an important role of the netrins during retinal angiogenesis. A comprehensive analysis of their roles might lead to new therapeutic strategies against pathological angiogenesis processes.
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