Immunoregulation in avascular regions of the eye: A role for the lens
The eye has long been considered an immune privileged site. Blood and lymphatic vessels are excluded from the central light path that passes through the cornea and the lens, and limited to more peripheral regions of the eye. Yet, immune cells are required to maintain tissue homeostasis and mediate the reparative responses to injury and pathogenic insults.
This webinar will focus on recent discoveries, which revealed that the lens, an avascular tissue in the anterior segment of the eye, plays an important role in activating, recruiting and regulating immune responses in the absence of an embedded vasculature.
The ciliary zonules, that link the lens to the vasculature-rich ciliary body, will be discussed as a major pathway by which immune cells can populate the surface of the lens. It will be shown that in response to corneal wounding, immune cells are recruited specifically to the anterior, cornea-facing surface of the lens. That these lens-associated immune cells include macrophages and GR-1+ immune cells suggests that they function as immunoregulators involved in maintaining homeostasis in the anterior segment of the eye following corneal wounding. We will examine the discovery that the lens was found to harbor a population of tissue resident immune cells, an immune cell type known to function as the earliest responders to tissue injury, and that these resident immune cells populate the lens during development and are maintained in the adult. Lens resident immune cells provide a key to the mechanism by which immune cells are activated to be recruited to the lens surface in response to cornea wounding, as well as play a likely role in the activation of both innate and adaptive immune responses to the lens that is observed when lens degeneration occurs.
Lastly, we will show that immune cells, including T-cells, macrophages, and myeloid cells with immunoregulatory properties, are recruited to the surface of the lens in the autoimmune disease Experimental Induced Uveitis (EAU). These lens associated immune cells populate all surfaces of the lens at the height of uveitis, where they remain linked through the resolution of EAU inflammation. The evidence presented will all point to the lens, located in the center of the eye and interfacing with the anterior, equatorial and posterior compartments of the eye, as a previously unappreciated regulator of inflammation in the immune privileged eye that is key to maintaining its homeostasis.
Sue Menko received her PhD from the University of Pennsylvania and her postdoctoral training at both the University of Pennsylvania and the University of Minnesota. She has held faculty positions at the University of Pennsylvania and Thomas Jefferson University, where she is now Professor and Vice Chair of the Department of Pathology, Anatomy and Cell Biology. Dr. Menko has chaired the Jefferson Committee on Research and co-founded the Wills Vision Research Center at Jefferson.
Over the course of her career, much of Dr. Menko’s research has focused on the signaling pathways that guide cell differentiation and development. Her findings have included the first evidence that integrin-dependent signals are required for undifferentiated cells to express their differentiated phenotype, which, in studies with the lens, were extended to show that a coordinated integrin/growth factor receptor pathway regulates the initiating signals of lens cell differentiation.
In more recent studies, Dr. Menko’s lab has investigated the response to lens wounding, examining the factors that determine whether the wound outcome is regenerative or fibrotic. These studies revealed that, despite being an avascular tissue, the lens harbors a population of resident immune cells that play an important role in its response to wounding. She found that both innate and adaptive immune responses were activated in response to lens cell degeneration, challenging the idea that the avascular property of the lens prevented it from being infiltrated by immune cells. This unexpected finding began a new area of research in Dr. Menko’s lab, which has led to the discovery that immune cells are specifically recruited to the surface of the lens following injury to the cornea and in response to the autoimmune disease uveitis. Many of these recruited lens-associated immune cells have immunomodulatory properties, evidence that they are immunoregulators involved in maintaining homeostasis in regions of the eye that lack an embedded vasculature.