Abstract
Purpose :
Exfoliation glaucoma (XFG) is the most common secondary form of open angle glaucoma. XFG is the ocular presentation of exfoliation syndrome (XFS), and LOXL1 contains SNPs that highly associate with XFG. LOXL1 is an amine oxidase that crosslinks elastin, collagens, and other fibrillary proteins to provide structure to tissues. We have shown that mixed 129S and C57 background mice with LOXL1 depletion have an enlarged Schlemm’s canal (SC) and higher IOPs in comparison to Loxl1+/- and Loxl1+/+ littermate mice. The purpose of this study is to compare the ocular and non-ocular phenotypes in Loxl1-/-, Loxl1+/-, and Loxl1+/+ mice backcrossed onto the C57BL/6 (C57) background.
Methods :
Mixed background mice were backcrossed for 6 generations (N6) onto a C57 background. Intraocular pressure (IOP) was measured using rebound tonometry. Gross dorsal and ventral images and body weights were obtained to investigate body size differences, prolapse prevalence, and elasticity of skin. The anatomy of the anterior compartment of the eyes was assessed for hallmark characteristics of elastosis and fibrillary material accumulation in the outflow pathway.
Results :
Backcrossing resulted in 98.5% C57 genetic background, and genotyping confirmed Loxl1+/+, Loxl1+/-, and Loxl1-/-. The mean IOPs of Loxl1-/-, Loxl1+/-, and Loxl1+/+ eyes averaged 18.8, 19.9, and 19.8 mmHg, respectively. Our preliminary findings indicate that the Loxl1-/- and the Loxl1+/- have enlarged SC areas compared to the Loxl1+/+. While the mice did not have significantly different body weights, the elasticity of the skin in the backcrossed N6 Loxl1-/- is greater than in the Loxl1+/- and Loxl1+/+ mice. Importantly, the prevalence of spontaneous anal prolapse in N6 Loxl1-/- mice was 60% before the age of 2 months old, making this mouse model of LOXL1 depletion impossible to study past the age of 2 months old.
Conclusions :
Loxl1-/- mice backcrossed onto C57s exhibit enlarged SC, greater skin elasticity, and high prevalence of anal prolapse when compared to the Loxl1+/-, Loxl1+/+, or mixed background Loxl1-/- mice, consistent with severe elastosis. Due to the prevalence of prolapse, this backcrossed Loxl1-/- mouse proves to be an unsustainable aging model for XFG, as the severity of elastosis is increased too much by a homogenous background.
This is a 2020 ARVO Annual Meeting abstract.