Local inhibition of glaucomatous mitochondrial dysfunction using an engineered annular sector microneedle

Area of Science:

• Biomedical Engineering
• Ophthalmology
• Molecular Biology

Background:

• Mitochondrial dysfunction contributes to glaucomatous trabecular meshwork (TM) degeneration.
• Increasing intracellular nicotinamide adenine dinucleotide (NAD+) levels can restore mitochondrial homeostasis and benefit glaucoma therapy.

Purpose of the Study:

• To develop a combinatorial strategy for glaucoma treatment by boosting intracellular NAD+ levels.
• To create a targeted drug delivery system for the TM using microneedle patches.

Main Methods:

• Co-delivery of nicotinamide (NAM) and the Nmnat1 gene encapsulated in lipid nanoparticles (Nmnat1-LNPs).
• Development of an annular sector-shaped microneedle patch (AS-MNs) for localized TM delivery.
• Evaluation of dual-loaded AS-MNs (Dual@AS-MNs) in a dexamethasone-induced mouse model of glaucoma.

Main Results:

• Nmnat1-LNPs and NAM synergistically reversed mitochondrial dysfunction in human trabecular meshwork cells (HTMCs).
• Dual@AS-MNs enhanced the bioavailability of Nmnat1 gene and NAM in TM tissue.
• Significant reduction in intraocular pressure and TM fibrosis observed in the glaucoma mouse model.

Conclusions:

• The study presents the first annular sector-shaped microneedle patch for targeted TM drug delivery.
• A promising new combinatorial strategy using Nmnat1 gene and NAM delivery for glaucoma treatment is proposed.
• The developed microneedle patch system shows therapeutic potential for glaucoma by addressing mitochondrial dysfunction and TM degeneration.