‘Hypothesis Article:Therapeutic effect of POL101 eyedrops, anti-VEGF
agents, in vitro and in vivo models’
Abstract
Background and Purpose: Choroidal neovascularization (CNV) is the
leading cause of blindness in patients with age-related macular
degeneration (AMD). Several studies reported increased levels of
vascular endothelial growth factor (VEGF) in retinal pigment epithelium
(RPE) from AMD patients. The aim of this study was to investigate the
efficacy of the VEGF-A targeted peptide nucleic acid (PNA) drug, POL101
eyedrops, in retinal pigment epithelial cell and laser-induced CNV
animal model. Experimental Approach: POL101 is a PNA based-Antisense
oligonucleotide (ASO) drug which chemically improved properties for
stability and delivery to tissue through nano-grade particle size. To
evaluate the efficacy of POL101, we performed to in vitro assay in
retinal pigment cell and Fundus fluorescein angiography (FFA), optical
coherence tomography (OCT) scanning, and electroretinography (ERG) in
CNV-induced lesion. Key Results: First, the efficacy of POL101 was
verified in ARPE-19 and HUVEC cells. And then, we confirmed that POL101
eyedrops was significantly decreased CNV area to 54.2% compared with
vehicle in laser-induced CNV lesion and reduced VEGF level in choroid
tissue without cellular apoptosis. Also, Photocoagulation demonstrated
that the average CNV lesion area was reduced and recovered retina
function in POL101 group. The mRNA expression of VEGF in mouse retina,
intracellular adhesion molecule-1 (ICAM-1), matrix metallopeptidases -2
(MMP-2) and 9 (MMP-9) were significantly reduced in POL101
eyedrops-treated group. Conclusion and Implications: In conclusion,
POL101 eyedrops was effectively suppressed VEGF-mediated CNV than
aflibercept and has the potential to be effective without side effects
and could replace biologics.