# IOP-Related Force and Failure in the Optic Nerve Head

> **NIH NIH R01** · LEGACY EMANUEL HOSPITAL AND HEALTH CENTER · 2020 · $590,809

## Abstract

Project Summary/Abstract
 In the previous project period we completed our 3D histomorphometric characterization of connective
tissue deformation and remodeling in early through end-stage monkey experimental glaucoma (EG). Based on
those findings, in this renewal proposal we will seek to identify important molecular and cellular components of
optic nerve head (ONH) connective tissue and retrolaminar myelin remodeling in monkey early experimental
glaucoma (EG). In so doing we will identify age-related differences in these phenomena and provide
unprecedented microscopic support for their early in vivo detection by optical coherence tomography (OCT).
 In Aim 1 we will phenotype the ONHs of young and old monkeys with unilateral early EG using quantitative
proteomic, immunohistochemistry (IHC), in situ hybridization (ISH) and electron microscopy (EM) techniques.
We hypothesize that connective tissue and retrolaminar myelin remodeling are core components of ONH aging
and glaucoma and will test predictions regarding their timing, and character in monkey early EG relative to the
development of retinal ganglion cell (RGC) cytoarchitecture disruption, alterations in the ONH constituent cells,
and the presence of wound healing, inflammation and monocyte/macrophage infiltration. In Aim 2 we will
explore our hypothesis that the pathophysiology of ONH aging overlaps with glaucoma by testing two
predictions regarding old vs young Control eye differences in the Aim 1 data: first that they will share important
features of EG vs Control eye differences in monkeys of all ages; and second that they will also share
important features of old vs young EG eye differences in monkey early EG. In Aim 3 we will accurately
colocalize Aim 1 IHC/ISH/EM findings to sacrifice-day OCT B-scans of the same eyes so as to provide light
and electron microscopic validation in monkeys for ONH OCT detection of early glaucoma damage in humans.
To accomplish these aims we will employ: state of the art quantitative iTRAQ Mass Spectroscopy; our novel
strategy for quantitative ONH IHC/ISH; quantitative transmission and scanning block face EM; precise
anatomic colocalization of each IHC/ISH paraffin and each EM vibratome section to OCT B-scans, retrolaminar
optic nerve (ON) axon counts, and sacrifice day OCT change-from-baseline data. All outcomes will be reported
in anatomically consistent, 30º degree ONH sectors that are oriented relative to the foveal-BMO axis.
 Aim 1 will generate the first quantitative proteomic characterization of the monkey ONH, peripapillary
scleral (pp-scleral), ON and retinal tissues in early EG. IHC/ISH and EM studies will demonstrate that
connective tissue and myelin remodeling are present at an early stage of RGC axonal insult. They will also
detect alterations in the ONH and pp-scleral tissues and cells that include proliferation, phagocytosis,
myofibroblast differentiation, wound healing, monocyte infiltration, and inflammation. Aim 2 will confirm that
proteomic,...

## Key facts

- **NIH application ID:** 9884768
- **Project number:** 5R01EY011610-23
- **Recipient organization:** LEGACY EMANUEL HOSPITAL AND HEALTH CENTER
- **Principal Investigator:** Claude F Burgoyne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $590,809
- **Award type:** 5
- **Project period:** 1998-07-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884768

## Citation

> US National Institutes of Health, RePORTER application 9884768, IOP-Related Force and Failure in the Optic Nerve Head (5R01EY011610-23). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9884768. Licensed CC0.

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