Targeting HDAC3 in the DBA/2J spontaneous mouse model of glaucoma
Heather M Schmitt1, Joshua A Grosser2, Cassandra L Schlamp3
1Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, United States; Department of Ophthalmology, Duke University, Durham, NC, United States.
Experimental Eye Research
|September 24, 2020
Summary
Targeting histone deacetylase-3 (HDAC3) did not prevent retinal ganglion cell (RGC) loss in a glaucoma model. However, inhibiting HDAC3 showed mild protection against cell loss in aged mice, suggesting other HDACs warrant investigation.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- High intraocular pressure (IOP) is a major risk factor for glaucoma, leading to retinal ganglion cell (RGC) death.
- Current treatments focus on lowering IOP, but direct RGC preservation strategies are lacking.
- Histone deacetylase-3 (HDAC3) is implicated in early cellular events preceding RGC death.
Purpose of the Study:
- To investigate whether targeting HDAC3 protects RGCs in the DBA/2J mouse model of spontaneous glaucoma.
- To assess the impact of HDAC3 inhibition on RGC survival, somatic cell loss, and optic nerve degeneration.
Main Methods:
- Utilized conditional knockout and pharmacological inhibition (RGFP966) of HDAC3.
- Employed the DBA/2J mouse model, a spontaneous glaucoma model.
- Evaluated RGC survival, somatic cell loss, and optic nerve integrity.
Main Results:
- Targeted ablation of HDAC3 did not protect RGCs from axonal degeneration or somatic cell death.
- HDAC3 inhibition with RGFP966 provided mild protection against somatic cell loss in aged DBA/2J mice.
- BRN3A expression loss and optic nerve degeneration were not prevented by HDAC3 targeting.
Conclusions:
- HDAC3 may not be a suitable therapeutic target for preventing RGC loss in this spontaneous glaucoma model.
- Further research into other class I HDACs is warranted for potential therapeutic strategies in chronic glaucoma.
- Mild protection observed with HDAC3 inhibition suggests a complex role in glaucoma pathogenesis.
