Weiming Mao
Indiana University-Purdue University-Indianapolis, IN·Pharmacology
Steroid drugs called glucocorticoids are widely used to treat eye inflammation. In many people, however, they raise the pressure inside the eye.
- Fields
Pharmacology
Medicine & Clinical Research
Biochemistry
- Topics
glaucoma
ocular hypertension
glucocorticoids
- Grants
- 1 known grant, through Jul 2027
What they work on
- Test whether activating canonical Wnt signaling prevents steroid-induced high eye pressure in mice, using Wnt reporter mice and conditional knockout mice that lack β-catenin, the pathway's key protein.
- Determine whether Wnt activation weakens the anti-inflammatory effects of glucocorticoids, using mouse models of uveitis, a type of eye inflammation.
- Test whether the Wnt blocker Dkk1 is elevated and Wnt signaling reduced in fluid and trabecular meshwork tissue from patients with glucocorticoid-induced glaucoma compared with non-glaucoma eyes.
- Test in paired human donor eyes perfused with dexamethasone whether the Wnt activator CHIR relieves high pressure and whether Dkk1 induces it.
- Define how a nuclear complex of β-catenin, the glucocorticoid receptor, HDAC1 and MeCP2 controls steroid-responsive genes, using RNA-seq, ATAC-seq, co-immunoprecipitation, mass spectrometry, FLIM-FRET and ChIP-qPCR.
More about the research
This side effect can lead to glucocorticoid-induced glaucoma, a form of vision loss. Pressure rises in about 40% of the general population and about 90% of patients with primary open-angle glaucoma, the most common glaucoma. The challenge is to block the pressure rise without losing the drugs' anti-inflammatory benefit.
Why it matters
The work could lead to safer ways to use glucocorticoids in eye disease, by preventing the pressure rise that causes steroid-induced glaucoma while keeping the drugs' anti-inflammatory effects. The Wnt activator being tested may serve as a lead compound for future drugs. Patients who need long-term steroid treatment for eye conditions could benefit.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Mihyun Nam
University of Colorado Denver/Anschutz Medical Campus, CO·Medicine & Clinical Research
Compare levels of advanced glycation end products (AGEs), sugar-damaged proteins, in trabecular meshwork tissue from primary open-angle glaucoma patients and healthy controls.
Carla Siegfried
Washington University in St Louis, MO·Medicine & Clinical Research
Compare gene expression in trabecular meshwork tissue from healthy donors and glaucoma patients at different stages, confirming key genes with RT-qPCR, in situ hybridization and Western blot, with focus on mitochondria and antioxidant defenses.
Shahid Husain
Medical University of South Carolina, SC·Pharmacology
Determine how class I and IIb histone deacetylases (HDACs), enzymes that tighten DNA packaging, contribute to retinal ganglion cell death in rats with ocular hypertension (high eye pressure).
The school
Indiana University-Purdue University-Indianapolis: 25 labs on PI Pages, $89M a year on research, 120 research doctorates a year.
More about Indiana University-Purdue University-Indianapolis
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