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Open Angle Glaucoma: Treatment01:27

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In open-angle glaucoma, the iridocorneal angle remains open, but the trabecular meshwork becomes stiff, slowing down the outflow of aqueous humor. This causes a buildup of aqueous humor in the anterior chamber, leading to a sudden increase in intraocular pressure. The treatment for open-angle glaucoma focuses on reducing the elevated intraocular pressure by either decreasing the secretion of aqueous humor or increasing its outflow.
Drugs such as carbonic anhydrase inhibitors, α2- and...
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MicroRNA-146a (miR-146a) delivery reduced intraocular pressure (IOP) in rats. This gene therapy approach shows promise for glaucoma treatment without adverse effects.

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Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Gene Therapy

Background:

  • Glaucoma is a leading cause of irreversible blindness.
  • Elevated intraocular pressure (IOP) is a primary risk factor for glaucoma.
  • Trabecular meshwork (TM) dysfunction contributes to IOP elevation.

Purpose of the Study:

  • To investigate the role of microRNA-146a (miR-146a) in trabecular meshwork (TM) cells.
  • To evaluate the effect of viral miR-146a delivery on intraocular pressure (IOP) in vivo.
  • To assess the safety and efficacy of miR-146a as a potential glaucoma gene therapy.

Main Methods:

  • Human TM cells were treated with miR-146a mimics or inhibitors and subjected to cyclic mechanical stress (CMS).
  • Gene expression was analyzed using quantitative polymerase chain reaction (qPCR).
  • Replication-deficient adenoviral and lentiviral vectors expressing miR-146a were delivered to rat anterior chambers, with IOP monitored via rebound tonometry.

Main Results:

  • miR-146a modulated gene expression related to outflow homeostasis in TM cells, both at baseline and under CMS.
  • Viral delivery of miR-146a via both adenoviral and lentiviral vectors led to sustained IOP reduction (2.6–4.4 mmHg).
  • Long-term follow-up (>8 months) confirmed sustained IOP lowering (4.4 ± 2.9 mmHg) with no observed inflammation or visual acuity deficits.

Conclusions:

  • Intracameral delivery of miR-146a effectively lowers IOP in rats.
  • This approach demonstrates a long-term IOP-lowering effect without significant adverse events.
  • miR-146a gene therapy represents a promising strategy for future glaucoma treatment.