Expression of Genes in Müller Cells Using an Experimental Model of Retinal Hypoxia.

Introduction: Müller glial cells typically activate to react to hypoxic tissue damage in several retinal diseases. We evaluated the response to a hypoxia-mimicking stimulus on the expression of a set of genes, known to contribute to eye morphogenesis and cell differentiation.

Materials And Methods: A MIO-M1 Müller cell line was cultured in a hypoxia-mimicking environment by the addition of cobalt chloride to the culture medium, followed by a recovery time in which we mimic restoration from the hypoxic insult. The HIF-1 protein and VEGF-A gene expression were quantified to verify the induction of a hypoxia-like state.

Results: Among the genes under study, we did not observe any difference in the expression levels of and during treatment; conversely, was overexpressed during recovery steps. The VEGF-A gene was strongly upregulated at both the CoCl and recovery time points. The transactivated isoform (TA) of the gene showed an overexpression in long-term exposure to the hypoxic stimulus with a further increase after recovery. . Our molecular analysis is able to describe the activation of a set of genes, never before described, that can drive the response to a hypoxia-like status. The improved comprehension of these cellular events will be useful for designing new therapeutical approaches for retinal pathologies.