Disruption of fibronectin fibrillogenesis affects intraocular pressure (IOP) in BALB/cJ mice

Increased deposition of fibronectin fibrils containing EDA+fibronectin by TGF[beta]2 is thought to be involved in the reduction of aqueous humor outflow across the trabecular meshwork (TM) of the eye and the elevation in intraocular pressure (IOP) observed in primary open angle glaucoma (POAG). Usin...

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Bibliographic Details
Published in:PloS one 2020-08, Vol.15 (8), p.e0237932-e0237932
Main Authors: Faralli, Jennifer A, Filla, Mark S, McDowell, Colleen M, Peters, Donna M
Format: Article
Language:English
Subjects:
Aqueous humour
Biology and Life Sciences
Cell culture
Collagen
Development and progression
Disruption
Experiments
Extracellular matrix
Eye (anatomy)
Fibrillogenesis
Fibronectin
Fibronectins
Glaucoma
Health aspects
Hypertension
Immunofluorescence
Injection
Intraocular pressure
Laboratories
Medicine
Medicine and Health Sciences
Microscopy
Pathology
Physiological aspects
Proteins
Public health
Reduction
Research and Analysis Methods
Western blotting
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Summary:Increased deposition of fibronectin fibrils containing EDA+fibronectin by TGF[beta]2 is thought to be involved in the reduction of aqueous humor outflow across the trabecular meshwork (TM) of the eye and the elevation in intraocular pressure (IOP) observed in primary open angle glaucoma (POAG). Using a fibronectin-binding peptide called FUD that can disrupt fibronectin fibrillogenesis, we examined if disrupting fibronectin fibrillogenesis would affect IOP in the TGF[beta]2 BALB/cJ mouse model of ocular hypertension. BALB/cJ mice that had been intravitreally injected with an adenovirus (Ad5) expressing a bioactive TGF[beta]2.sup.226/228 showed a significant increase in IOP after 2 weeks. When 1[mu]M FUD was injected intracamerally into mice 2 weeks post Ad5-TGF[beta]2 injection, FUD significantly reduced IOP after 2 days. Neither mutated FUD (mFUD) nor PBS had any effect on IOP. Four days after FUD was injected, IOP returned to pre-FUD injection levels. In the absence of TGF[beta]2, intracameral injection of FUD had no effect on IOP. Western blotting of mouse anterior segments expressing TGF[beta]2 showed that FUD decreased fibronectin levels 2 days after intracameral injection (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0237932