Abstract
Purpose :
Long term intravitreously anti-VEGF treatment may lead to fibrosis. To determine whether PDGF-B inhibition reduces subretinal fibrosis, we developed an AAV2 expressing sPDGFRB and tested in a laser induced choidal neovascularization (CNV) model.
Methods :
AAV2.AcGFP, AAV2.sFlt1, and AAV2.sPDGFRB were subretinally injected with 1 µl (1x109 vg) into C57/Bl6 mice. To assess efficacy, CNV was induced by argon laser (Iridex) one month after subretinal injection. CNV area was measured two weeks after laser injury by choroidal flatmount. To evaluate safety, retinal thickness and histology were assessed 4 months after subretinal injection.
Results :
The mean CNV area was signficantly smaller in the AAV2.sFlt1 (20.1± 2.3 ×103 µm2, p<0.05), and AAV2.sPDGFRB (14.2±1.5 ×103 µm2, p<0.0001) group than in control mice treated with AAV2.AcGFP (26.2±2.2×103 µm2). The mean fibrosis area in the AAV2.sFlt1 (12.2±1.2×103 µm2, p>0.05), and AAV2.sPDGFRB (10.3±1.7×103 µm2, p<0.05) groups were all lower than control mice treated with AAV2. AcGFP (17.9 ± 1.8×103 µm2). Retinal thickness was not affected by AAV2.sPDGFRB. N=10 in each group. Statistical analysis was performed using one-way ANOVA.
Conclusions :
AAV2.sPDGFRB may be a novel gene therapy for wet AMD due to significant angiogenesis and fibrosis inhibition.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.