Abstract
Purpose :
Chorodial neovascularization (CNV) is a defining characteristic feature of neovascular age-related macular degeneration (nAMD) that frequently results in irrversible vision loss. The current strategies for the treatment of nAMD are mainly based on neutralizing vascular endothelial growth factor (VEGF). However, anti-VEGF therapies are often associated with subretinal fibrosis that eventually leads to damages in macula. It was the aim of this study to investigate wheter an anti-fibrotic and anti-angiogenic protein CCN5 can a potential novel stratey for the treatment of nAMD with a capability to inhibit CNV and fiborsis stimultaneously.
Methods :
To induce CNV in mouse eyes, laser photocoagulation was utilized. At 5 days after laser-induced CNV, recombinant adeno-associated virus serotype 2 encoding CCN5 (rAAV2-CCN5), rAAV2-virus-like-particle (VLP), and bevacizumab were administered via intravitreal injection. One week after injection, fundus fluorescent angiography (FFA), immunostaining, and cell counting were performed to determine rAAV2-CCN5 inhibits CNV leakage, retinal gliosis, change of retinal pigmented epithelium (RPE) cell morphology, and epithelial-mesenchymal transition (EMT) on RPE.
Results :
Our data demonstrated that rAAV2-CCN5, but not a control viral vector, rAAV2-VLP, prominently attenuated both CNV lesions and angiogenesis. Bevacizumab, which was utilized as a positive control, exhibites similar effects on CNV lesion and angiogenesis. Upon laser photocoagualtion, RPE cells underwent significant morphological changes including cellular enlargement and loss of hexagonality. rAAV2-CCN5 significantly normalized these morphological defects, while bevacizuumab did marginally. Laser photocoagulation also led to fibrotic deformation in RPE cells through inducing EMT, which was completely blocked by rAAV2-CCN5. In a striking contrast, Bevacizumab as well ase rAAV2-VLP failed to exhibit any effects on EMT.
Conclusions :
Our data demonstrate that rAAV2-CCN5 can inhibit CNV and EMT in RPE cells that are induced by laser photocoagulation in mice. Therefore, we suggest that rAAV2-CCN5 can be a safer yet efficient therapeutic modality for nAMD.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.