# Paradigms of Wound Healing and Fibrosis in the Eye

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2020 · $526,083

## Abstract

Abstract/Project Summary
Immune privilege of the eye results from the need to keep vasculature from the central light path where it
would impair vision. Therefore, organs and tissues of the eye like the cornea, have developed alternative
mechanisms of immune surveillance to protect them and in response to injury or tissue pathogenesis. In the
CNS, novel immune surveillance adaptations have been discovered for protection and repair that
demonstrate a state of immune quiescence. In the cornea, which can tolerate foreign antigens, there are
immune cells that surveille it in the peripheral regions of the cornea, the aqueous humor, and the tears. The
lens has remained an enigma in terms of immune surveillance and protection. We now show that, like other
tissues, the lens has developed mechanisms of immune surveillance to protect it throughout a lifetime and to
respond to stresses and injury while maintaining its transparency. Since dysregulation of immune
surveillance is tightly linked to development of fibrosis, it is possible that the immune cells that associate with
the lens may be an unexplored cause of cataract and posterior capsule opacification (PCO).
 We have discovered resident immune cells (β2 integrin/CD45+) in the lens, that are activated upon
mock cataract surgery and have essential functions in regenerative repair of the wound area. These cells are
susceptible to being diverted from this role, and induced to acquire a myofibroblast phenotype, the cell type
that underlies fibrotic PCO. The resident immune cells first appear in the lens during development, delivered
by the tunica vasculosa, a vasculature that surrounds the developing lens; however, this vasculature
degenerates after birth. It was assumed that there are no active sources of immune cells that could surveille
and protect the adult lens during homeostasis and in response to stress, injury, or pathogenesis. However,
we discovered that
 in response to lens dysgenesis (N-cad∆lens mice) or corneal debridement wounding, an extrinsic immune
surveillance mechanism is activated resulting in the recruitment of immune cells to the lens. These immune
cells move between the ciliary body and the lens across the ciliary zonules that connect them, in the absence
of a vasculature. Over time, these immune cells can acquire a myofibroblast phenotype and lead to lens
opacity. Studies of eyes from these N-cad∆lens mice also revealed that there is an immune response to lens
dysgenesis in the central cornea, vitreous, and retina.
 We will build on these findings in three specific aims expected to elucidate how extrinsic immune cells
are able to travel to the lens, how the immune system is activated to protect the lens in response to corneal
injury and to protect the cornea in response to lens dysgenesis, and how immune cells that surveille the lens
in response to its damage/pathogenesis, or that of another tissue, may lead to cataract and PCO.

## Key facts

- **NIH application ID:** 9952390
- **Project number:** 5R01EY021784-10
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** A. Sue Menko
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $526,083
- **Award type:** 5
- **Project period:** 2011-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952390

## Citation

> US National Institutes of Health, RePORTER application 9952390, Paradigms of Wound Healing and Fibrosis in the Eye (5R01EY021784-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952390. Licensed CC0.

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