# Impaired phospholipid metabolism in glaucoma

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $383,750

## Abstract

PROJECT SUMMARY / ABSTRACT
The overall goal of this proposal is to better understand impaired phospholipid metabolism in the trabecular
meshwork (TM) tissue in glaucoma. The term phospholipid (PL) here refers to primarily three classes of lipids:
phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE). A better understanding of
PL metabolism in the anterior eye chamber will provide insight into glaucoma pathology and facilitate the
development of new, disease-modifying intervention strategies. Our long-term goal is to develop better
intervention strategies for glaucoma by understanding the pathological changes in metabolism, and in
particular PL metabolism, in the glaucomatous anterior chamber. The absence of a comprehensive knowledge
of PL changes in diseased compared to healthy aqueous humor (AH) or TM represents a critical barrier to
progress in treating and preventing glaucoma. The proposed research is based on our extensive preliminary
studies performed over the past seven years.
We discovered a substantial decrease in PS and a general increase in PE lipid species in glaucomatous TM
compared to controls. This has followed rigorous analyses of levels and activity of enzymes in a
comprehensive and unbiased manner, demonstrating their alteration at critical branch points. Thus, we
propose to comprehensively investigate all PL interconversion enzymes in an unbiased manner. We also found
vastly different fold changes differing only slightly with respect to acyl-chain length (or structural features)
between control and glaucomatous TM or AH suggesting that the functions of transport proteins are potentially
aberrant in glaucomatous TM. We propose to investigate selected PL transport proteins in glaucomatous TM
tissue. Pathologic TM tissue consistently demonstrates altered biophysical properties, for example an elevated
elastic modulus. Our central hypothesis is that phospholipid metabolism is impaired in glaucoma, affecting
biophysical properties of the trabecular meshwork and contributing to its pathophysiology. In Aim 1 we will test
whether PL interconversion enzymes are altered in glaucoma, In Aim 2 we will evaluate whether PL transport
proteins are altered in glaucoma, and finally in Aim 3 we will determine whether restoring specific PLs that
become deficient in the diseased state can improve the biophysical properties of glaucomatous TM. We will
also evaluate correlation of biophysical properties with IOP lowering in murine models. We will use routine
(Western blot, immunosorbent assays) and innovative methods analytical techniques such as kinetic
histochemistry employing imaging mass spectrometry. The proposal also has brought forth a conceptual
innovation that is PL metabolism impairment in TM in glaucoma. The expected outcome of the proposed
research is the identification of aberrations in specific enzymes of PL metabolizing pathways and in PL
molecules that dysregulate biophysical properties of TM. These new insig...

## Key facts

- **NIH application ID:** 10114486
- **Project number:** 1R01EY031292-01A1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Sanjoy K Bhattacharya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,750
- **Award type:** 1
- **Project period:** 2021-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114486

## Citation

> US National Institutes of Health, RePORTER application 10114486, Impaired phospholipid metabolism in glaucoma (1R01EY031292-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10114486. Licensed CC0.

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