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Open Access Green as soon as Postprint is submitted to ZB.
PKG activity causes photoreceptor cell death in two retinitis pigmentosa models.
J. Neurochem. 108, 796-810 (2009)
Photoreceptor degeneration in retinitis pigmentosa is one of the leading causes of hereditary blindness in the developed world. Although causative genetic mutations have been elucidated in many cases, the underlying neuronal degeneration mechanisms are still unknown. Here, we show that activation of cGMP-dependent protein kinase (PKG) hallmarks photoreceptor degeneration in rd1 and rd2 human homologous mouse models. When induced in wild-type retinae, PKG activity was both necessary and sufficient to trigger cGMP-mediated photoreceptor cell death. Target-specific, pharmacological inhibition of PKG activity in both rd1 and rd2 retinae strongly reduced photoreceptor cell death in organotypic retinal explants. Likewise, inhibition of PKG in vivo, using three different application paradigms, resulted in robust photoreceptor protection in the rd1 retina. These findings suggest a pivotal role for PKG activity in cGMP-mediated photoreceptor degeneration mechanisms and highlight the importance of PKG as a novel target for the pharmacological intervention in RP.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
calcium; cGK; cGMP; nitric oxide; rd1 mouse; retina; dependent protein-kinase; vasodilator-stimulated phosphoprotein; inherited retinal degenerations; rod cgmp-phosphodiesterase; nucleotide-gated channels; d-cis-diltiazem; cyclic-gmp; mouse retina; rd mouse; guanosine-monophosphate
ISSN (print) / ISBN
0022-3042
e-ISSN
1471-4159
Journal
Journal of Neurochemistry
Quellenangaben
Volume: 108,
Issue: 3,
Pages: 796-810
Publisher
Wiley
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Metabolomics & Proteomics (CF-MPC)