# Microtubule Deficit in Glaucoma

> **NIH NIH R21** · HUNTER COLLEGE · 2022 · $92,140

## Abstract

Our objective is to identify new molecular targets for early detection and treatment of glaucoma. During the
progression of glaucoma, the axons of the retinal ganglion cells (RGCs) are gradually lost. Our hypothesis is that
axonal microtubules (MTs) are critically involved in the process. We demonstrated recently, using second-
harmonic generation (SHG) microscopy as a novel retinal imaging and DBA mice as a model of inherited
glaucoma, that axonal MTs degrade more rapidly than the loss of RGC axons (‘MT deficit’) and MT deficit is
spatially correlated with axonal atrophy. Our results suggest that MT deficit is a new pathology of early glaucoma,
which may have a common pathogenic origin as the loss of RGC axons. Here we aim to explore the capacities
of newly discovered pathology beyond early detection. We hypothesize that MT deficit may represent a reversible
stage suitable for therapeutic intervention and provide the molecular substrate for the RGC’s sensitivity to the
elevated IOP triggering the pathological response. To test this notion, the mechanism of MT deficit must be
elucidated. As a potential target, we will interrogate the posttranslational modifications (PTMs) of axonal MTs,
also known as the tubulin codes, which modulate the interaction between MTs and MT-associated proteins
(MAPs). Our research will show how MT PTMs are altered during glaucoma and whether the change is correlated
with MT deficit. Also, we will test MT deficit as an endpoint marker of the RGC viability evaluating the efficacy of
therapeutic treatments. We will analyze the DBA retina receiving an increased level of NAD+ to protect the RGC
axons. Our research can yield valuable insights into the mechanism of MT deficit and open a new line of
questions toward improved glaucoma therapy.

## Key facts

- **NIH application ID:** 10468950
- **Project number:** 5R21EY033047-02
- **Recipient organization:** HUNTER COLLEGE
- **Principal Investigator:** Hyungsik Lim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $92,140
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468950

## Citation

> US National Institutes of Health, RePORTER application 10468950, Microtubule Deficit in Glaucoma (5R21EY033047-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468950. Licensed CC0.

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