Abstract
Purpose :
Vascular endothelial growth factor (VEGF) is a key down-stream mediator of choroidal neovascularization (CNV) and the target of intravitreal anti-VEGF therapy in neovascular age-related macular degeneration (nAMD). Photobiomodulation (PBM) targets mitochondria and has the potential to modulate the up-stream hypoxic and pro-inflammatory drivers of nAMD. We investigated the effect of PBM laser on size and leakage of choroidal neovascular membranes, VEGF levels, and retinal inflammation in a rodent model of laser-induced CNV.
Methods :
CNV was induced using a 532 nm fd Nd:YAG laser. Rats received either PBM laser or sham treatment every 3 days from 6 days prior and 12 days after induction of CNV. The treated group received 100 mW/cm2 of 670 nm PBM laser treatment for 90 seconds per eye. The sham group received the aiming beam only for 90 seconds per eye. Fluorescein angiography (FFA) and spectral domain optical coherence tomography (SD-OCT) analysis was performed at 7 and 14 days after induction for analysis of CNV size and permeability. Rats were then killed, and eyes processed for retinal flatmount immunohistochemistry of the endothelial marker, isolectin-B4 for secondary analysis of membrane size, and counterstained with IBA1 for analysis of microglial activity. Some rats were killed at day 3 and a 5 mm punch of the retina-RPE-choroid complex was used to measure VEGF levels with an enzyme linked immunosorbent assay. Statistical significance was determined by two-sample Welch’s t-test or Chi-Squared test.
Results :
PBM-treated eyes had significantly reduced isolectin-B4 staining (p = 0.01), smaller lesion volume on SD-OCT (p = 0.01), and modulation of capillary leakage on FFA at 14 days compared to sham-treated eyes (p = 0.00001). These features were coupled with significantly less microglial cell infiltration at the lesion site (p=0.01). There was no significant difference in VEGF levels (p = 0.92).
Conclusions :
PBM laser promoted regression and normalization of vascular barrier function in this rat model of laser-induced CNV. This was not associated with lower VEGF, suggesting an alternative mechanism. Reduction in retinal inflammation may contribute to this observed effect. Further translational research could potentially target clinical nAMD and assess the effect of retinal PBM laser as an adjunctive therapy to routine intravitreal anti-VEGF.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.