Differential gene expression profiling after conditional Müller-cell ablation in a novel transgenic model.

PURPOSE

Müller cells, the principal glial cells in the mammalian retina, play an important role in the maintenance of retinal homeostasis. Recent reports suggest that Müller-cell dysfunction may contribute to the pathogenesis of retinal diseases such as idiopathic macular telangiectasia type 2. In the present study, we used microarray to compare retinae isolated from transgenic mice in which the Müller cells of adult mice retinae can be selectively ablated with control mice.

METHODS

Retinae were isolated 1 week, 1 month, and 3 months after tamoxifen-induced selective Müller-cell ablation and microarray were performed with Affymatrix microarrays. Differentially expressed (DE) genes, temporal trends of DE genes, and pathway analysis were conducted. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the results.

RESULTS

Strong upregulation of mRNA of proteins involved in gliosis, apoptosis, and neurotrophism was found 1 week after ablation and their related pathways such as the apoptotic and Jak/Stat pathways were identified. Three months after induced Müller-cell ablation, Müller-cell metabolic pathways and vasculopathy-related pathways such as genes involved in glycolysis and tight junctions were downregulated. qRT-PCR analysis showed consistent expression trends of selected genes.

CONCLUSIONS

The results were generally consistent with the previous morphologic findings in this model, in which photoreceptor degeneration soon after Müller-cell ablation, accompanied by blood-retinal barrier breakdown and subsequent retinal neovascularization were reported. These results are consistent with a significant contribution of Müller-cell dysfunction on retinal neuronal injury and vascular pathology at the mRNA level.