Abstract
Purpose :
Matriptase, a cell surface serine protease, is critical for function of several epithelia. Matriptase null mice die 1-2 days after birth due to decreased epidermal barrier function. Hypomorphic mice (low matriptase) have a mild transient epidermal barrier defect in pups but have a normal lifespan allowing studies of functionality in adults. Our purpose is to determine the effects of matriptase gene deletion on the eye and lacrimal gland in adult mice.
Methods :
C57BL/6J-Matriptase hypomorphic and littermate control mice at 4-6, 11-12 and 13.5 months of age were sacrificed and eyes and lacrimal glands removed, fixed, embedded in epon-araldite and sectioned. Corneal epithelial thickness (cross sections through the pupil) was measured at 15 points across the central cornea. Corneal epithelial sheets were processed from both groups and Langerhans cells (dendritic cells) stained with a Langerin specific PE conjugated primary antibody. Eyes also were examined by slit lamp, and scanning EM. Mice also were infected with Pseudomonas aeruginosa and their response to infection scored for disease, and photographed using a slit lamp.
Results :
Measuring corneal thickness revealed that matriptase hypomorphic mice of 6 months of age had a significantly thicker corneal epithelium when compared with control mice. Similar measurements of older mice showed no differences between the two groups. Photographs taken with a slit lamp did not reveal any noticeable differences in corneal or ocular surface morphology between mice at any age. However, scanning EM showed differences in corneal surface morphology and irregularities in structure in the 4-6 month vs older aged hypomorphic vs control mice. Hypomorphic vs control mice of younger age also had a two-fold increase in Langerin positive cells in the peripheral cornea; and, lacrimal glands differed from controls in that glands exhibited patches of abnormal vacuolated acinar cells and the presence of an inflammatory infiltrate. Infected mice responded similarly to eye infection, but only hypomorphic mice exhibited swollen facial features and ruffled fur.
Conclusions :
In young vs older mice with low levels of matriptase we observed: a significant increase in corneal thickness, irregular surface cells, increased Langerhans cells, lacrimal gland abnormalities, and a worsened response to P. aeruginosa infection.
This is a 2021 ARVO Annual Meeting abstract.