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Nina Riddell, Sheila Gillard Crewther, Melanie Murphy, Loretta Giummarra, Pierre Faou, David Crewther; Retina/RPE proteome profiles in the chick model of optically-induced refractive error. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5479.
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Several exploratory transcriptome studies have profiled gene expression in the widely used chick model of refractive error, however, relatively little is known about corresponding proteome changes. Thus, this study used an exploratory label-free relative quantification approach to profile protein expression in the chick retina/RPE following 6 and 48hrs of defocus-induced myopia and hyperopia.
Chicks were raised from post-hatch day 5 with monocular +10D or -10D lenses, or No Lens. Following 6 and 48hrs, five chicks per lens-group were anesthetized and biometric measures were collected. Retina/RPE sections were then removed from the posterior eyecup and prepared for analysis by LC-ESI-MS/MS on a LTQ-orbitrap Elite (Thermo-Scientific). Raw data was processed using MaxQuant. Differentially-expressed proteins were identified using t-test (FDR<0.05) in Perseus, and Reactome pathway expression changes were identified using Gene Set Enrichment Analysis (GSEA; FDR<0.05).
A large number of proteins were differentially-expressed in both negative (327 at 6hrs & 252 at 48hrs) and positive (162 at 6hrs & 542 at 48hrs) lens groups relative to age-matched controls. These single protein expression changes were highly similar across the lens groups, with only two proteins (E1BZE1/AHSG & R4GFD0/PSME4) differentially-expressed in a sign-of-defocus dependent manner. Pathways related to ribosomal protein expression were down-regulated in both lens groups at 6hrs. Further pathways related to energy metabolism, SLC-mediated transmembrane transport, insulin secretion, GABA synthesis/release/re-uptake, and hemostasis were down-regulated in the 6hr negative lens group only. The same pathways were down-regulated over time in normally developing animals.
Similarities across negative and positive lens groups suggest that most of the measured expression changes were responses to non-specific factors (e.g. blur or physiological stress). Although GSEA confirmed the early involvement of several pathways previously hypothesized to play a role in myopia induction (e.g. insulin, GABA, & energy metabolism), the results also suggest that expression changes in these pathways may reflect an acceleration of the normal development program. Further research investigating this interplay with normal development may help to elucidate the mechanisms driving these expression changes and clarify cross-study disparities.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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