PuSH - Publikationsserver des Helmholtz Zentrums München: Proteomic profiling suggests central role of STAT signaling during retinal degeneration in the<em> rd10</em> mouse model.

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Ly, A. ; Merl-Pham, J. ; Priller, M. ; Gruhn, F. ; Senninger, N. ; Ueffing, M. ; Hauck, S.M.

Proteomic profiling suggests central role of STAT signaling during retinal degeneration in the rd10 mouse model.

J. Proteome Res. 15, 1350-1359 (2016)

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The rd10 mouse is a model of retinitis pigmentosa characterized by the dysfunction of a rod-photoreceptor-specific phosphodiesterase. Compared to the rd1 mouse, retinal degeneration in the rd10 mouse begins later in age with a milder phenotype, making it ideal for investigating cell death and neuroprotective mechanisms. Alterations in the rd10 retina proteome at pre-, peak-, and post-degenerative time points were examined using a modified high-recovery filter-aided sample preparation (FASP) method in combination with label-free quantitative mass spectrometry, generating a proteomic dataset on almost 3000 proteins. Our data confirmed a period of protein expression similar to age-matched wild-type mice pre-degeneration, with decreases in proteins associated with phototransduction and increases in signaling proteins at peak- and post-degenerative stages. 57 proteins were differentially expressed in the rd10 retinae during peak-degeneration compared to wild-type mice after stringent FDR correction (q<0.05). Network analysis separated these proteins into a cluster of downregulated photoreceptor proteins, and one of upregulated signaling proteins centered around GFAP, STAT3, and STAT1. This is the first study to identify alterations in STAT1 in the rd10 mouse, which were confirmed with gene expression and immunoblotting experiments underpinning the efficacy of our approach. This unique proteomic dataset on protein dynamics during retinal degeneration could serve as an information source for vision research in the future.

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