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Loss of Corneal Raver2 Expression in Aniridia Associated Keratopathy

Das, S. K.; Carroll, L.; Holt, D.; zhang, X.; Uehara, H.; Archer, B.; Ambati, J.; Ambati, B. K.

2020-02-22 developmental biology
10.1101/2020.02.21.959585 bioRxiv
Show abstract

PurposeThe aim of this study was to evaluate downstream factors of Pax6 associated with the aniridic corneal phenotype. We characterize the ocular expression of Raver2, a novel heterogeneous ribonucleoprotein (hnRNP). MethodsGenome wide microarrays of corneal RNA from non-aniridic mice (C57BL/6J and MRL/MpJ) and corneas from aniridia model, Pax6+/- (SEY) mice were performed. Raver2 expression profiles were validated using qPCR and western blot. Raver2 immunohistochemistry on corneas of Pax6+/- mice and aniridic humans were compared to control specimens, and insitu-hybridization was used to analyze developmental expression of Raver2. ResultsMicroarray analysis of corneal RNA identified Raver2 as the gene with the strongest differential expression profile across non-aniridic and aniridic mouse strains. Consistent with mouse data, we found that Raver2 is expressed at high levels in healthy human corneal epithelium, and is downregulated in the corneas of human aniridia patients. ConclusionsThese findings suggest that Raver2 has an evolutionarily conserved developmental role downstream of Pax6 in corneal development and maintenance.

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