# Mechanisms of Formation of Pseudoexfoliation Material on Human Surgical Lens Capsules

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $194,375

## Abstract

PROJECT SUMMARY/ ABSTRACT
Exfoliation syndrome is a systemic disease of the elastic fibers. The manifestation of this disease in the eye is
Pseudoexfoliation Glaucoma (XFG), which is the most common identifiable cause of glaucoma, the most
aggressive, and the one harder to treat. The disease is characterized by the formation of amyloid-like deposits
by various tissues of the anterior segment of the human eye. In particular, the material is more prominently
deposited on the anterior surface of the lens, between the iris and the lens, at the pupillary border. The material
is easily recognized by the ophthalmologist during a regular examination and it is dubbed as “a dandruff-like
material”. Its presence is the base for the diagnostic of the disease. It is widely accepted that the mechanical
friction exerted between the iris and the lens during the opening and closing of the pupil, leads to dislodgement
and release of the material into the aqueous humor. During the outflow of this fluid, the material is carried to the
trabecular meshwork, causing clogging and a consequent elevated IOP.
Proteomics on the composition of the material revealed the presence of a number of components. Among them,
some, such as Clusterin (CLU) and ApoE, have been known to be associated with the β-amyloid plaques
characteristic of Alzheimer disease. No many studies on XFG have been conducted To date, seven genes have
been linked to the XFG, with LOXL1 being the first and best studied. But very little is known about how this
material is formed and no attempts to reproduce its formation are available. Also, the XFM has not been
observed in any animal species, including nonhuman primates.
In this application, we propose to address this need. Because this material is only formed in humans, we devised
a novel strategy to conduct the study on human lens, more precisely on the most anterior region, where the
material is clinically observed. This region of the lens is routinely peeled off (and discarded) by ophthalmology
surgeons during cataract surgery. Termed “lens capsule” (LC), it comprises the 14 µm lens capsule together
with the single layer of epithelial cells underneath. Thus, we will develop and characterize these organotypic
cultures form the discarded surgical LCs to begin studying how the XFM is formed. We will focus on two major
relevant components, CLU and LOXL1. We will modulate their production by gene transfer, and expose them,
not only to XFG stressors, but to conditioned media secreted by the lens proximal tissues, specially by the Iris
Pigment Epithelium (IPE). We will evaluate formation of XFG-like deposits by confocal microscopy and their
effect on the elastin and fibrillin networks in the insoluble ECM by immunohistochemistry. We have initial
feasibility data and although important challenges need to be overcome, we believe that the new system could
provide an invaluable tool to the field and render important information about the disease. The understanding
g...

## Key facts

- **NIH application ID:** 9993529
- **Project number:** 5R21EY030608-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Hua Mei
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993529

## Citation

> US National Institutes of Health, RePORTER application 9993529, Mechanisms of Formation of Pseudoexfoliation Material on Human Surgical Lens Capsules (5R21EY030608-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993529. Licensed CC0.

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