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Paulo Vinicius Svidnicki, Monica B Melo, Jose Paulo C Vasconcellos, Shi Song Rong, Anna Larson, John Simmons Borchert, Janey L Wiggs; APEX1 as a new candidate gene for glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1614. doi: https://doi.org/.
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To determine if APEX1 gene is a candidate gene for glaucoma. Taking to account that rare variants were found in exome studies in glaucoma patients, one of these variants were even segregating with the disease in an early onset open angle glaucoma family. To do so, we performed functional studies to evaluate the effects of knocking out the APEX1 gene in Zebrafish (Danio rerio).
Exome sequencing was performed in a Brazilian family with juvenile open-angle glaucoma. Sanger sequencing of 180 non-related glaucoma patients also from Brazil was also performed. Exome chip array of a set of USA glaucoma patients was also verified in search for APEX1 variants. The research followed the principles enounced in the Declaration of Helsinki.For the functional study, Zebrafish were maintained in accordance to established protocols. The MEEI Animal Committee approved all experiments. APEX1 gene was knocked out using translation blocking morpholino technique.
In total, nine different rare variants in APEX1 were found through Exome and Sanger sequence analysis. Morpholino-induced suppression of APEX1 generated reduced eye size in Zebrafish, besides underdeveloped lens and disorganized layers of the retina. The specificity of the MO was tested and confirmed by co-injection of human APEX1 mRNA.
We have some data that indicate that APEX1 could be involved in glaucoma and/or eye development features. Our studies are yet in progress to evaluate this hypothesis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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