Gene therapy for glaucoma: Targeting key mechanisms.

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Glaucoma is a leading cause of irreversible blindness due to progressive retinal ganglion cell (RGC) degeneration.
• Current treatments, primarily lowering intraocular pressure (IOP) with eye drops, face challenges in efficacy and patient compliance.
• Surgical interventions for resistant cases are invasive and carry risks.

Purpose of the Study:

• To review current gene therapy strategies for glaucoma, focusing on reducing IOP and preventing RGC death.
• To explore mechanisms underlying elevated IOP and RGC degeneration in glaucoma.
• To highlight research priorities for advancing gene therapy in glaucoma clinical trials.

Main Methods:

• Review of existing literature on gene therapy mechanisms and preclinical/clinical studies for glaucoma.
• Categorization of gene therapy approaches based on their targets: IOP reduction and neuroprotection.
• Analysis of strategies for enhancing conventional outflow, targeting fibrosis, regulating aqueous humor, and neuroprotection.

Main Results:

• Gene therapy approaches for IOP reduction include enhancing extracellular matrix turnover, targeting fibrosis, regulating aqueous humor production, and myocilin-specific gene therapy.
• Neuroprotective strategies involve targeting neurotrophic factors, reducing oxidative stress and mitochondrial dysfunction, and preventing Wallerian degeneration.
• Key research priorities include refining delivery vectors and improving transgene regulation for clinical translation.

Conclusions:

• Gene therapy presents a significant potential for long-term glaucoma management by addressing underlying molecular causes.
• Targeting both IOP and RGC survival is crucial for effective disease control.
• Further research and development in delivery systems and gene regulation are essential for successful clinical application of gene therapies for glaucoma.