Induction of Immune Surveillance of the Dysmorphogenic Lens

The lens has been considered to be an immune privileged site not susceptible to the immune processes normally associated with tissue injury and wound repair. However, as greater insight into the immune surveillance process is gained, we have reevaluated the concept of immune privilege. Our studies using an N-cadherin lens-specific conditional knockout mouse, N-cad^Δlens, show that loss of this cell-cell junctional protein leads to lens degeneration, necrosis and fibrotic change, postnatally. The degeneration of this tissue induces an immune response resulting in immune cells populating the lens that contribute to the development of fibrosis. Additionally, we demonstrate that the lens is connected to the lymphatic system, with LYVE(+) labeling reaching the lens along the suspensory ligaments that connect the lens to the ciliary body, providing a potential mechanism for the immune circulation. Importantly, we observe that degeneration of the lens activates an immune response throughout the eye, including cornea, vitreous humor, and retina, suggesting a coordinated protective response in the visual system to defects of a component tissue. These studies demonstrate that lens degeneration induces an immune response that can contribute to the fibrosis that often accompanies lens dysgenesis, a consideration for understanding organ system response to injury.