The Histone Deacetylase Inhibitor AN7, Attenuates Choroidal Neovascularization in a Mouse Model

Area of Science:

• Ophthalmology
• Vascular Biology
• Pharmacology

Background:

• Choroidal neovascularization (CNV) is a significant complication of age-related macular degeneration, leading to substantial vision loss.
• Current treatments for CNV have limitations, necessitating the exploration of novel therapeutic strategies.

Purpose of the Study:

• To investigate the efficacy of systemic Butyroyloxymethyl-diethyl phosphate (AN7), a histone deacetylase inhibitor (HDACi), in a mouse model of laser-induced CNV.
• To evaluate the impact of AN7 on CNV area, vascular leakage, and key molecular markers associated with neovascularization.

Main Methods:

• A laser-induced CNV mouse model was utilized.
• Systemic administration of AN7 was compared to control and intravitreal bevacizumab treatments.
• CNV area and vascular leakage were assessed using choroidal flatmounts and fluorescein angiography.
• Expression levels of VEGF, FGF-2, and CD31 were analyzed.
• In vitro studies examined AN7's effect on retinal pigmented epithelium (RPE) cell tight junctions under hypoxic conditions.

Main Results:

• Systemic AN7 treatment significantly reduced CNV area and vascular leakage.
• The efficacy of AN7 in reducing CNV area was comparable to intravitreal bevacizumab.
• AN7 treatment led to decreased expression of VEGF, FGF-2, and CD31 at the laser lesion site.
• In vitro, AN7 preserved RPE cell tight junction integrity and reduced permeability during hypoxia.

Conclusions:

• Systemic AN7 demonstrates significant therapeutic potential for treating CNV.
• AN7's ability to reduce neovascularization and vascular leakage warrants further investigation as a novel treatment for CNV.
• AN7 may offer a new therapeutic avenue for conditions characterized by aberrant blood vessel growth.