Abstract
Müller cells are critical for retinal function and neuronal survival but can become detrimental in response to retinal ischemia and increased oxidative stress. Elevated oxidative stress increases expression of the mitochondrial enzyme frataxin in the retina, and its overexpression is neuroprotective after ischemia. Whether frataxin expression in Müller cells might improve their function and protect neurons after ischemia is unknown. The aim of this study was to evaluate the effect of frataxin overexpression in Müller cells on neuronal survival after retinal ischemia/reperfusion in the mouse in vivo. Retinal ischemia/reperfusion was induced in mice overexpressing frataxin in Müller cells by transient elevation of intraocular pressure. Retinal ganglion cells survival was determined 14 days after lesion. Expression of frataxin, antioxidant enzymes, growth factors and inflammation markers was determined with qRT-PCR, Western blotting and immunohistochemistry 24 hours after lesion. Following lesion, there was a 65% increase in the number of surviving RGCs in frataxin overexpressing mice. Improved survival was associated with increased expression of the antioxidant enzymes Gpx1 and Sod1 as well as the growth factors Cntf and Lif. Additionally, microglial activation was decreased in these mice. Therefore, support of Müller cell function constitutes a feasible approach to reduce neuronal degeneration after ischemia.
Highlights
One key element of the pathologic alteration in retinal ischemia/reperfusion injury is the generation of excessive reactive oxygen species (ROS) during reperfusion
To prove the cellular localization of human FXN, retinal slices were co-stained with anti-GFP and the Müller cell-specific marker glutamine synthetase (GS)
We found an increased RGC survival in transgenic mice overexpressing FXN
Summary
One key element of the pathologic alteration in retinal ischemia/reperfusion injury is the generation of excessive reactive oxygen species (ROS) during reperfusion. Müller cells (MG) are the predominant glia in the vertebrate retina, expand the entire retina forming a structural scaffolding and have cell contacts to all neuronal cell types in the different retinal layers They can form a functional unit with a more critical role than for astrocytes, which are restricted to the nerve fiber layer[1]. We found an increased expression of endogenous FXN in the mouse retina 24 hours after an ischemic lesion, indicating that FXN is involved in neuroprotective mechanisms in response to ischemic retinal injury[16]. To further evaluate the cellular mechanisms involved in the FXN-mediated neuroprotection in the ischemic retina and the putative role of Müller cells, here we used a conditional transgenic mouse model overexpressing the human FXN gene in these cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
