# Studies in Glaucomatous Optic Nerve Damage

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $479,097

## Abstract

Project Summary
 Understanding cellular mechanisms of intraocular pressure (IOP)-induced axonal injury will help develop new
glaucoma treatments that protect the optic nerve. Our Controlled Elevation of IOP (CEI) model produces optic
nerve head (ONH) gene expression changes and optic nerve (ON) damage that parallel those observed in
chronic models. An RNAseq time-course analysis has revealed that IOP produces early activation of several
major pathways and specific recovery of their components. We have now developed a method of creating
awake CEI (aCEI) exposures in conscious rats using an indwelling anterior chamber cannula that is externally
accessible. This will allow us to study events of chronic glaucoma, which occurs over years, in the relatively
short time frame of a laboratory setting.
 In Specific Aim 1, we will (a) demonstrate that an 8-hour aCEI at 40 mmHg will produce little to no injury
compared to 50 mmHg, (b) show that a non-injurious, lower IOP will produce ONH gene expression changes
that are less than, but qualitatively similar, to those seen with an injurious, higher IOP and (c) show that
exposure to aCEI in elderly animals will produce greater injury than the same level of pressure in adult
animals.
 Specific Aim 2 will show that (a) the timing of a second, injurious aCEI following an initial, similar exposure
will affect additivity of the axonal injury and (b) the timing of a repeat, injurious aCEI will affect ONH gene
expression and recovery.
 Specific Aim 3 will demonstrate that (a) repeat aCEI can be used to model “chronic” glaucomatous optic
nerve damage, (b) an eye with pressure-induced optic nerve injury will be more susceptible to subsequent IOP
exposure than an eye without prior injury and (c) IOP fluctuations produce more injury than the same level of
IOP maintained at a steady state for the same duration.
 These studies in unanesthetized animals use levels of IOP that, relative to normal, mean rat IOP, are
comparable to human glaucoma, and will provide the most accurate representation of this aspect of the human
disease possible in laboratory rats. They will provide unique insights into cellular mechanisms of chronic
glaucomatous optic nerve damage and allow study of previously unapproachable aspects of this chronic
disease.

## Key facts

- **NIH application ID:** 10436849
- **Project number:** 5R01EY010145-23
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** JOHN C MORRISON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $479,097
- **Award type:** 5
- **Project period:** 1993-04-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436849

## Citation

> US National Institutes of Health, RePORTER application 10436849, Studies in Glaucomatous Optic Nerve Damage (5R01EY010145-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436849. Licensed CC0.

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