Integral role for lysyl oxidase‐like‐1 in conventional outflow tissue function and behavior

Autor: W. Daniel Stamer, Michael A. Hauser, Guorong Li, William M. Johnson, Maria Gomez-Caraballo, Jenny Cui, Todd L. Fleming, Iris Navarro, Heather Schmitt, Chanyoung Lee, C. Ross Ethier, Sina Farsiu, Joseph M. Sherwood, Michael H. Elliott
Rok vydání: 2020
Předmět:
Zdroj: FASEB J
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.202000702rr
Popis: Lysyl oxidase like-1 (LOXL1), a vital crosslinking enzyme in elastin fiber maintenance, is essential for the stability and strength of elastic vessels and tissues. Variants in the LOXL1 locus associate with a dramatic increase in risk of exfoliation syndrome, a systemic fibrillopathy, which often presents with ocular hypertension and exfoliation glaucoma. We examined the role of LOXL1 in conventional outflow function, the prime regulator of intraocular pressure. Using Loxl1(−/−), Loxl1(+/−) and Loxl1(+/+) mice, we observed an inverse relationship between LOXL1 expression and intraocular pressure, which worsened with age. Elevated intraocular pressure in Loxl1(−/−) mice was associated with a larger globe, decreased ocular compliance, increased outflow facility, extracellular matrix abnormalities, and dilated intrascleral veins, yet no dilation of arteries or capillaries. Interestingly, in living Loxl1(−/−) mouse eyes, Schlemm’s canal was less susceptible to collapse when challenged with acute elevations in intraocular pressure, suggesting elevated episcleral venous pressure. Thus, LOXL1 expression is required for normal intraocular pressure control, while ablation results in altered extracellular matrix repair/homeostasis and conventional outflow physiology. Dilation of Schlemm’s canal and distal veins, but not arteries, is consistent with key structural and functional roles for elastin in low-pressure vessels subjected to cyclical mechanical stress.
Databáze: OpenAIRE
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