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

© 2020 Federation of American Societies for Experimental Biology..

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 (XFS), a systemic fibrillopathy, which often presents with ocular hypertension and exfoliation glaucoma (XFG). We examined the role of LOXL1 in conventional outflow function, the prime regulator of intraocular pressure (IOP). Using Loxl1-/- , Loxl1+/- , and Loxl1+/+ mice, we observed an inverse relationship between LOXL1 expression and IOP, which worsened with age. Elevated IOP in Loxl1-/- mice was associated with a larger globe, decreased ocular compliance, increased outflow facility, extracellular matrix (ECM) abnormalities, and dilated intrascleral veins, yet, no dilation of arteries or capillaries. Interestingly, in living Loxl1-/- mouse eyes, Schlemm's canal (SC) was less susceptible to collapse when challenged with acute elevations in IOP, suggesting elevated episcleral venous pressure (EVP). Thus, LOXL1 expression is required for normal IOP control, while ablation results in altered ECM repair/homeostasis and conventional outflow physiology. Dilation of SC 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:34

Enthalten in:

FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 34(2020), 8 vom: 15. Aug., Seite 10762-10777

Sprache:

Englisch

Beteiligte Personen:

Li, Guorong [VerfasserIn]
Schmitt, Heather [VerfasserIn]
Johnson, William M [VerfasserIn]
Lee, Chanyoung [VerfasserIn]
Navarro, Iris [VerfasserIn]
Cui, Jenny [VerfasserIn]
Fleming, Todd [VerfasserIn]
Gomez-Caraballo, María [VerfasserIn]
Elliott, Michael H [VerfasserIn]
Sherwood, Joseph M [VerfasserIn]
Hauser, Michael A [VerfasserIn]
Farsiu, Sina [VerfasserIn]
Ethier, C Ross [VerfasserIn]
Stamer, W Daniel [VerfasserIn]

Links:

Volltext

Themen:

Amino Acid Oxidoreductases
Crosslinking
EC 1.4.-
EC 1.4.3.-
Elastin
Extracellular matrix
Fibrosis
Intraocular pressure
Journal Article
Loxl1 protein, mouse
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Schlemm's canal

Anmerkungen:

Date Completed 01.03.2021

Date Revised 02.08.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1096/fj.202000702RR

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312014856