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Kepeng Ou, Jiahui Wu, Jian Liu, Sebastian Wesselborg, Andrew D Dick, Stefan Schrader, Lei Liu; The regulatory role of hypoxic macroglia on endothelial cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5397. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
In addition to their primary role in supporting neurons in the retina, macroglial cell and their activators (Müller cells and astrocytes) are involved in the pathogenesis of various retinal vascular diseases. However, the extent of their contribution and cellular and molecular mechanisms therein are incompletely understood. Our initial aim was to characterize the angiogenic potential of Müller cells and astrocytes under hypoxic conditions.
To mimic retinal ischemia in vitro, human Müller cells (MIO-M1) and primary retinal astrocytes were cultured under hypoxic (1% O2) or normoxic conditions (21% O2) for 24 hours. The expression of angiogenic factors was examined using RT-qPCR and ELISA. Human Umbilical Vein Endothelial Cells (HUVEC) tube formation induced by conditioned medium was used to assess the angiogenic effects of macroglia.
The results show that both mRNA and protein levels of vascular endothelial growth factor (VEGF) and angiopoietin-like 4 (ANGPTL4) in both Müller cells and astrocytes were markedly increased under hypoxic conditions. In contrast, anti-angiogenic factor, soluble fms-like tyrosine kinase-1 (sFlt-1), remained unaltered. Furthermore, conditioned medium from hypoxic Müller cells resulted in a 65% increase (P<0.01) of HUVEC tube formation not exhibited by conditioned medium of hypoxic astrocytes.
Our data infers a regulatory role of retinal macroglia on endothelial cells when hypoxic Müller cells but not astrocytes enhance angiogenesis. Further investigation is required to define the angiogenic role of Müller cells in retinal vascular diseases.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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