Anesthetic Preconditioning as Endogenous Neuroprotection in Glaucoma

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Glaucoma causes blindness through Retinal Ganglion Cell (RGC) death, often preceded by dysfunction.
• Current treatments targeting intraocular pressure (IOP) are insufficient for neuroprotection.
• Developing effective, safe IOP-independent neuroprotective agents for glaucoma is a significant challenge.

Purpose of the Study:

• To investigate the neuroprotective potential of preconditioning RGCs with retrobulbar lidocaine in a mouse model of glaucoma.
• To assess the long-term effects of lidocaine on RGC survival, function, and related protein expression.

Main Methods:

• DBA/2J mice with spontaneous glaucoma received retrobulbar lidocaine injections in one eye.
• Axonal transport was assessed using cholera toxin B.
• Long-term effects (9 months) evaluated RGC electrical responsiveness (PERG), IOP, protein expression (BDNF, TrkB, PSD95, GFAP, Synaptophysin, GAPDH), and RGC density.

Main Results:

• Lidocaine treatment did not affect IOP but increased TrkB expression and decreased GFAP expression.
• RGC survival improved by 35%, and PERG function was preserved.
• Retrobulbar lidocaine preconditioning demonstrated significant neuroprotective effects.

Conclusions:

• Minimally invasive retrobulbar lidocaine can extend the lifespan of functional RGCs in early-stage mouse glaucoma.
• Lidocaine offers a safe, inexpensive, and FDA-approved option for neuroprotection in glaucoma.
• This study suggests a promising adjuvant therapy for glaucoma management.