Abstract
Purpose :
To examine how immune protection is delivered to the lens during development, how immune surveillance is provided in response to both endogenous and exogenous insults to lens tissue, and the potential for cells providing immune protection to become disease-causing myofibroblasts.
Methods :
Cryosections of chick embryo eyes at embryonic D15 and adult mouse eyes at 1D post-corneal wounding were examined for the presence of immune cells and the path they take to the lens by high-resolution confocal imaging using various immune cell-specific antibodies in combination with antibody to fibrillin or MAGP1, matrix components of the ciliary body, and perlecan, a matrix component of the lens capsule.
Results :
Our previous studies show that in response to lens dysgenesis due to conditional knockout of N-cadherin (N-cadDlens mouse), immune cells enter the lens proper and are induced to become myofibroblasts. Our studies of the chick embryo lens show that immune cells travel between the ciliary body and the lens during development along the fibrillin-rich ciliary zonules. In addition, we found that by embryonic D15 resident MHC II+ dendritic cells become located in the region of the equatorial epithelial, adjacent to where the zonules insert into the lens capsule, inserted between the lens epithelial cells. Immune surveillance of the lens continues in the adult. Like in the embryo, immune cells are detected along the ciliary zonules between the ciliary body in the lens. In response to a cornea debridement wound, immune cells are activated to travel along the ciliary zonules and then migrate anteriorly along the MAGP1-rich zonules that extend along the equatorial towards the anterior aspects of the lens capsule.
Conclusions :
In the absence of a vasculature the lens has adapted a unique mechanism for immune surveillance to protect the lens. Immune surveillance of the lens that is activated in response to cornea injury, suggests this is the pathway by which immune cells populate the dysgenic lens where they have the potential to acquire the myofibroblast phenotype associated with fibrosis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.