Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization

Area of Science:

• Ophthalmology
• Neuroscience
• Regenerative Medicine

Background:

• Choroidal neovascularization (CNV) is a primary cause of vision loss in wet age-related macular degeneration (AMD).
• The role of the ocular sympathetic nervous system in CNV development is not fully understood.
• Modulating sympathetic activity presents a potential therapeutic target for wet AMD.

Purpose of the Study:

• To investigate the impact of modulating ocular sympathetic activity on the progression of laser-induced CNV in a rat model.
• To evaluate both pharmacological and surgical interventions targeting the sympathetic nervous system.

Main Methods:

• Laser-induced CNV model in Brown Norway rats.
• Pharmacological modulation using isoproterenol (agonist) and propranolol (antagonist) eye drops.
• Surgical intervention via internal carotid nerve (ICN) transection at various time points post-injury.
• Quantification of CNV volume using fluorescein angiography, OCT, and 3D confocal reconstruction.
• Measurement of VEGF protein levels via ELISA.

Main Results:

• Blocking ocular sympathetic activity (pharmacologically or surgically) reduced CNV lesion volume by 70-75% (P < 0.001).
• Stimulating sympathetic activity with isoproterenol showed a smaller reduction (27%, P < 0.05).
• VEGF protein levels were elevated across treatment groups (P < 0.01).
• Surgical denervation inhibited CNV progression irrespective of timing (immediately or 7 days post-injury).

Conclusions:

• Both surgical and pharmacological blockade of ocular sympathetic activity effectively inhibit CNV progression in a preclinical model.
• Electrical blockade of the internal carotid nerve (ICN) warrants investigation as a bioelectronic medicine strategy for wet AMD treatment.