# Biomechanical and genetic effects on glaucoma progression

> **NIH NIH K08** · PURDUE UNIVERSITY · 2021 · $164,602

## Abstract

PROJECT SUMMARY / ABSTRACT
Glaucoma is a group of progressive optic neuropathies that together are leading causes of irreversible vision
loss. The pathogenic mechanisms that lead to its hallmark, progressive retinal ganglion cell (RGC) death, are
unknown, but key risk factors include increased intraocular pressure (IOP). Vision loss often persists with
current IOP-lowering treatments, thus urgent needs exist both for better understanding of glaucomatous
mechanisms and improved glaucoma therapies other than IOP reduction. Based on our clinical findings that
vision is preserved markedly longer in dogs with open-angle glaucoma (OAG) caused by spontaneous
mutation of the matrix metalloproteinase-encoding gene ADAMTS10 than in dogs with other forms of
glaucoma, and our novel biomechanical findings, I hypothesize that inter-individual differences in
biomechanical effects of IOP on optic nerve head (ONH) contribute strongly to glaucoma progression and
individuals' differential susceptibilities to it. My long-term goal is to develop novel therapeutic approaches to
modify ONH and scleral biomechanics, to permit and improve preservation of optic nerve (ON) and RGC
function in glaucoma patients. This multidisciplinary, collaborative translational study will test the central
hypothesis that ADAMTS10-mutant individuals have high compliance of ONH, peripapillary sclera, and
extracellular matrix (ECM) preceding and during glaucoma development, that protects ON axons even when
IOP is chronically elevated. Specific Aims: Using clinically-relevant translational canine chronic glaucoma
models, including ADAMTS10-OAG, I propose 3 Aims: In Aim 1, I will test the hypothesis that that ADAMTS10
mutation mitigates IOP-induced ON damage. In Aims 2 and 3, I will test the hypotheses that ONH and
peripapillary sclera in eyes with ADAMTS10-OAG (Aim 2: tissue level) and the peripapillary scleral fibroblasts,
astrocytes, and lamina cribrosa (LC) cells, and their ECM exhibit more compliant properties (Aim 3: cellular
and ECM level). In addition, in Aim 3, I will test if ECM derived from ADAMTS10-mutant LC cells and
peripapillary scleral fibroblasts modulates biomechanical properties of non-mutant cells. Significance: Based
on extensive preliminary data and using large animal spontaneous glaucoma models, we will provide the first
test of the effects of inherently-altered biomechanical properties of peripapillary sclera and ONH, and their
potential interactions with elevated IOP, in determining the course of glaucoma progression. Innovation: I will
determine 1) novel neuroprotective biomechanical properties of the ONH and peripapillary sclera in glaucoma
in `real disease' models, and 2) compliance of astrocytes, LC cells, scleral fibroblasts, and their ECM and cell-
ECM interactions in pathogenic mechanisms. My innovation includes our novel, well-established cross-
disciplinary collaborative mentoring team with a strong track record in successful translational research in
ocular b...

## Key facts

- **NIH application ID:** 10145700
- **Project number:** 5K08EY030950-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Shin Ae Park
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $164,602
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145700

## Citation

> US National Institutes of Health, RePORTER application 10145700, Biomechanical and genetic effects on glaucoma progression (5K08EY030950-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10145700. Licensed CC0.

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