Purchase this article with an account.
Weiyong Shen, Marcus Fruttiger, Ling Zhu, Sook H. Chung, Nigel L. Barnett, An Nguyen, Nathan Coorey, Murray Killingsworth, Mark C. Gillies; Selective Ablation Of Müller Cells Leads To Photoreceptor Injury, Blood-Retinal Barrier Breakdown And Deep Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1854.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The link between Müller glial dysfunction, retinal neuronal injury and vascular abnormalities remains poorly understood. This study aims to characterize retinal changes in a transgenic model of selective disruption of Müller cells.
Transgenic mice were produced using a DNA construct containing a Müller cell-specific promoter driving a tamoxifen (TMX)-inducible form of Cre recombinase (CreERT2). The cell-specific promoter contained a fragment of regulatory region of the retinaldehyde binding protein 1 gene (Rlbp1). Rlbp1-CreER transgenic mice were crossed with Rosa-LacZ mice for Müller-specific gene expression and further crossed with Rosa-DTA176 mice for cell ablation. Changes in the retinal glia, neurons and microvasculature were investigated after switching on the DTA176 toxic gene expression.
Crossing Rlbp1-CreER mice with Rosa-LacZ mice resulted in LacZ expression in Müller cells but not other types of retinal cells. Crossing Rlbp1-CreER mice with Rosa-DTA176 transgenic mice led to selective, patchy ablation of Müller cells alternating with areas of Müller glial activation, photoreceptor apoptosis, blood-retinal barrier (BRB) breakdown, vascular telangiectasis and deep retinal neovascularization. Müller cell apoptosis was observed at 1 day after TMX induction and followed by photoreceptor damage from 3 to 10 days after Müller glial ablation. However, severe vascular leakage and deep retinal neovascularization occurred much later, predominantly 2 months after induction of the DTA176 toxin production by TMX. Photoreceptor injury and vascular changes were accompanied by differential expression of cyclin D3, P27, erythropoietin, espin, vascular endothelial growth factor and pigment epithelium-derived factor.
Selective disruption of Müller cells leads to photoreceptor injury, BRB breakdown and retinal neovascularization. This model will be useful for studying the interactions between Müller glial dysfunction, photoreceptor injury and retinal vascular abnormalities in a number of retinal diseases such as diabetic retinopathy and macular telangeictasis type 2.
This PDF is available to Subscribers Only