ABCA1 Deletion Does Not Affect Aqueous Humor Outflow Function in Mice

TL;DR

Deleting the ABCA1 gene in mice does not change eye pressure or fluid drainage, but affects a related signaling pathway.

Contribution

This study shows ABCA1 deletion does not impact aqueous humor outflow function, but alters Cav1/eNOS/NO pathway expression.

Findings

ABCA1 deletion in mice does not alter anterior segment morphology or intraocular pressure.

Aqueous humor outflow facility remains unchanged in Abca1−/− mice.

Cav1 and eNOS expressions are upregulated in the outflow tissue of Abca1−/− mice.

Abstract

ATP binding cassette transporter A1 (ABCA1) is a candidate gene within a POAG susceptibility locus by GWAS analysis, and it is involved in IOP modulation via the Cav1/eNOS/NO signaling pathway. We aim to examine the phenotype of ABCA1 deletion in the ABCA1 gene knockout (Abca1−/−) mice.

The anterior segments of Abca1−/− eyes were imaged by slit-lamp microscopy and anterior segment OCT. IOPs were measured by rebound tonometry. By perfusing enucleated eyes at various pressures, the aqueous humor outflow facility was determined. The mRNA expressions of ABCA1, Cav1, and eNOS were measured by RT-qPCR. The protein expressions were analyzed by western blot and immunofluorescence staining.

There was no significant difference in the anterior segment morphology of Abca1−/− mice. IOP and aqueous humor outflow facility did not change in Abca1−/− mice compared with wild-type mice. mRNA and protein expressions of ABCA1 were significantly lower in the outflow tissue of Abca1−/− eyes. The expressions of Cav1 and eNOS were both significantly upregulated in the outflow tissue of Abca1−/− eyes.

ABCA1 deletion does not affect IOP and aqueous humor outflow function but the Cav1/eNOS/NO pathway is changed in Abca1−/− mice. The function of ABCA1 in aqueous humor outflow still requires further research.

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