Abstract
Purpose :
Nonexudative (dry) AMD is the predominant type leading to chronic vision loss and manifests as geographic atrophy (GA) in late stages, while exudative (wet) AMD is characterized by choroidal neovascularization (CNV) and results in acute vision loss due to neovascular leakage. Long-term treatment with anti-vascular endothelial growth factor (VEGF) agents, such as aflibercept, by frequent intravitreal injection is effective in inhibiting CNV leakage in wet AMD patients. Previous clinical studies found repeated use of anti-VEGF agents increased the risk of GA development in wet AMD patients. This study investigated effects of repeated use of anti-VEGF agents in mouse retina.
Methods :
Female C57BL/6J mice of 14 weeks old were used. 2μL aflibercept (40mg/mL) was injected into the vitreous cavity of the mice weekly. Mice in the control group were intravitreally injected with 2μL sterile phosphate-buffered saline (PBS) (n=8 per group). After treatment for 8 weeks, mice were sacrificed. Retina and choroid were isolated for RNA extraction to study the expression of multiple genes linked to AMD pathogenesis by quantitative real-time polymerase chain reaction (qRT-PCR). Gapdh was set as a reference control. Unpaired Student’s t-test was performed for statistical analysis and data were presented as mean+/-SEM.
Results :
In comparison with the PBS group, the retina with intravitreal aflibercept treatment for 8 weeks showed a marked increase in the expression of multiple AMD risk genes, including Dcn (p<0.0001), Apoe (p=0.0009), Cx3cr1 (p=0.0003), Cfh (p=0.004), Sod2 (p=0.0011), Ccl2 (p<0.0001) and Ccr2 (p=0.0004), while no significant alterations were observed in Vegf (p=0.2115), Mmp2 (p=0.1387) and Vtn (p=0.9156). Conversely, in the choroid, intravitreal aflibercept treatment remarkably decreased the expression of Apoe (p<0.0001), while no pronounced changes were observed in Ccr2 (p=0.7725), Cfh (p=0.6931), Ccl2 (p=0.7945), Cx3cr1 (p=0.4423), Vtn (p=0.2261), Vegf (p=0.1658) with Sod2, Dcn, and Mmp2 remaining undetectable (Figure 1).
Conclusions :
Our results suggest that long-term intravitreal injection of anti-VEGF agents may contribute to the expression changes in AMD associated genes.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.