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Jadwiga Oczos, Barbara Kloeckener-Gruissem, Wolfgang Berger, Christian Grimm; Paraoxonase-1 (PON1) in retinal physiology and pathophysiology. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6081. doi: https://doi.org/.
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Paraoxonase-1 (PON1) has anti-oxidant activity and is thought to prevent or reduce oxidation of low density lipoprotein (LDL). Recently, we have shown association between age-related macular degeneration (AMD) and single nucleotide polymorphisms in the upstream regulatory region of the PON1 gene. Little information on expression and the role of PON1 in the retinal physiology is available. The aim of our work was to study Pon1 expression pattern in the mouse retina and in primary mouse retinal pigment epithelial (mRPE) cells. Another objective was to determine the role of PON1 in retinal physiology by comparing Pon1 knockout (Pon1-/-) with control mice.
Laser Capture Microscopy (LCM) was used to obtain tissue from different retinal layers (RPE, ONL, INL, GCL). Primary mRPE cells were isolated from adult mice and cultured in vitro. Gene expression was assessed by PCR and RT-PCR. Pon1-/- and control mice were exposed to 15000 lux of white light for 2 hours to induce severe photoreceptor degeneration. Retinal morphology was evaluated by light microscopy.
Pon1 was strongly expressed in RPE, which has been demonstrated in tissue isolated by LCM and in freshly isolated mouse RPE. Pon1 expression was downregulated in primary mRPE cells after 1 day in culture and could not be restored by compounds known to up-regulate Pon1 expression. No phenotype was observed in Pon1-/- mice up to 13 months of age. Pon1-/- and control mice were similarly susceptible to light induced photoreceptor degeneration.
Pon1 is strongly expressed in the RPE of the mouse eye in vivo, but its expression is quickly down-regulated in primary mRPE cells in culture. Absence of PON1 did not induce an obvious phenotype suggesting that PON1 may not be required for the development and maintenance of a normally layered retina. A potential involvement of PON1 in the internalization of LDL and/or oxidized LDL into RPE cells will be tested in vivo.
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