Investigative ophthalmology & visual scienceJan 22, 2026

Gene Therapy Using AAV-DJ to Reduce Myocilin for Treating Myocilin-Linked Glaucoma

Updated Feb 16, 2026

Abstract

-mediated silencing resulted in significant reductions in myocilin accumulation and intraocular pressure (IOP) in a glaucoma mouse model.

MYOC-targeting short-hairpin RNA effectively reduced myocilin accumulation and markers of endoplasmic reticulum stress in trabecular meshwork cells.
The treatment prevented age-dependent increases in IOP and preserved aqueous humor outflow facility in young Tg-MYOCP370L mice.
In aged Tg-MYOCP370L mice, AAV-DJ also lowered IOP and improved outflow facility.
Retinal ganglion cell survival and visual function were maintained following AAV-DJ treatment.

Simplified

PURPOSE: To evaluate the therapeutic efficacy of an adeno-associated virus serotype DJ () vector delivering -targeting short-hairpin RNA (shMYOC) in a MYOCP370L transgenic glaucoma mouse model (Tg-MYOCP370L) for the treatment of open-angle glaucoma (OAG) associated with MYOC mutations.

METHODS: An AAV-DJ vector, selected for its high transduction efficiency and tropism for trabecular meshwork (TM), was used to deliver shMYOC via a transpupillary intravitreal approach in Tg-MYOCP370L mice. Post-treatment evaluations included myocilin accumulation, ER stress marker expression, intraocular pressure (IOP), aqueous humor outflow facility, retinal ganglion cell (RGC) survival, and visual function.

RESULTS: AAV-DJ-shMYOC markedly reduced myocilin accumulation and ER stress markers in TM cells in vivo, effectively preventing age-dependent IOP elevation, preserving aqueous humor outflow facility, and maintaining RGC survival and visual function in young Tg-MYOCP370L mice. In aged Tg-MYOCP370L mice, AAV-DJ-mediated MYOC silencing similarly lowered IOP and improved outflow facility.

CONCLUSIONS: AAV-DJ-mediated MYOC silencing effectively alleviated glaucomatous pathology in Tg-MYOCP370L mice, highlighting its potential as a gene therapy strategy for myocilin-associated glaucoma.

Key numbers

21.05 nL/min/mm Hg

IOP Reduction in Young Tg-Mice

Outflow facility measured at 8 months post-injection.

652.1 cells per 0.3 mm visual field

RGC Density Preservation

Mean density compared to 544.7 cells in control eyes.

0.2848 cycles/deg

Visual Function Improvement

Average optomotor response acuity compared to 0.1828 cycles/deg in controls.

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Abstract

Key numbers

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