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

ABSTRACT: 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 and label-free mass spectrometry, generating a unique 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. 123 proteins were differentially expressed the rd10 retinae during peak-degeneration compared to wild-type mice. 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. This finding proves the efficacy of our approach, and that this dataset could serve as an information source for protein alterations in retinal degeneration.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Retina

DISEASE(S): Retinitis Pigmentosa

SUBMITTER: Juliane Merl-Pham  

LAB HEAD: Stefanie M. Hauck

PROVIDER: PXD002584 | Pride | 2016-03-21

REPOSITORIES: Pride