Publications by authors named "Andrea F Glück"

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The cGMP-Dependent Protein Kinase 2 Contributes to Cone Photoreceptor Degeneration in the -Deficient Mouse Model of Achromatopsia.

Int J Mol Sci 2020 Dec 23;22(1). Epub 2020 Dec 23.

Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-University, 81377 Munich, Germany.

Mutations in the gene, which encodes the A subunit of the cyclic guanosine monophosphate (cGMP)-gated cation channel in cone photoreceptor outer segments, cause total colour blindness, also referred to as achromatopsia. Cones lacking this channel protein are non-functional, accumulate high levels of the second messenger cGMP and degenerate over time after induction of ER stress. The cell death mechanisms that lead to loss of affected cones are only partially understood. Here, we explored the disease mechanisms in the knockout (KO) mouse model of achromatopsia. We found that another important effector of cGMP, the cGMP-dependent protein kinase 2 (Prkg2) is crucially involved in cGMP cytotoxicity of cones in KO mice. Virus-mediated knockdown or genetic ablation of in KO mice counteracted degeneration and preserved the number of cones. Analysis of markers of endoplasmic reticulum stress and unfolded protein response confirmed that induction of these processes in KO cones also depends on Prkg2. In conclusion, we identified Prkg2 as a novel key mediator of cone photoreceptor degeneration in achromatopsia. Our data suggest that this cGMP mediator could be a novel pharmacological target for future neuroprotective therapies.
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December 2020