Altered Ocular Fibrillin Microfibril Composition in Mice With a Glaucoma-Causing Mutation of Adamts10.
Invest Ophthalmol Vis Sci
; 62(10): 26, 2021 08 02.
Article
in En
| MEDLINE
| ID: mdl-34424262
ABSTRACT
Purpose:
Previously, we identified a G661R mutation of ADAMTS10 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif 10) as being disease causative in a colony of Beagles with inherited primary open-angle glaucoma (POAG). Mutations in ADAMTS10 are known to cause Weill-Marchesani syndrome (WMS), which is also caused by mutations in the fibrillin-1 gene (FBN1), suggesting functional linkage between ADAMTS10 and fibrillin-1, the principal component of microfibrils. Here, we established a mouse line with the G661R mutation of Adamts10 (Adamts10G661R/G661R) to determine if they develop features of WMS and alterations of ocular fibrillin microfibrils.Methods:
Intraocular pressure (IOP) was measured using a TonoLab rebound tonometer. Central cornea thickness (CCT), anterior chamber depth (ACD) and axial length (AL) of the eye were examined by spectral-domain optical coherence tomography. Sagittal eye sections from mice at postnatal day 10 (P10) and at 3 and 24 months of age were stained with antibodies against fibrillin-1, fibrillin-2, and ADAMTS10.Results:
IOP was not elevated in Adamts10G661R/G661R mice. Adamts10G661R/G661R mice had smaller bodies, thicker CCT, and shallower ACD compared to wild-type mice but normal AL. Adamts10G661R/G661R mice displayed persistent fibrillin-2 and enhanced fibrillin-1 immunofluorescence in the lens zonules and in the hyaloid vasculature and its remnants in the vitreous.Conclusions:
Adamts10G661R/G661R mice recapitulate the short stature and ocular phenotypes of WMS. The altered fibrillin-1 and fibrillin-2 immunoactivity in Adamts10G661R/G661R mice suggests that the G661R mutation of Adamts10 perturbs regulation of the fibrillin isotype composition of microfibrils in the mouse eye.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Glaucoma, Open-Angle
/
Microfibrils
/
ADAMTS Proteins
/
Fibrillins
/
Anterior Chamber
/
Mutation
Limits:
Animals
Language:
En
Journal:
Invest Ophthalmol Vis Sci
Year:
2021
Type:
Article
Affiliation country:
United States