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Eoijong seo, Jeong A Choi, Jae-Young Koh, Young Hee Yoon; Aflibercept ameliorates retinal pericyte loss and improves nonperfusion in streptozotocin-induced diabetic mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2715.
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Pericyte dysfunctions and blood-retinal barrier disruptions are hallmarks of early stage of diabetic retinopathy (DR). Aflibercept is widely used anti-vascular endothelial growth factor (VEGF) agent in advanced DR but the effect in pericyte survival and early DR is still unclear. We conducted the experimental study to confirm the protective effect of aflibercept on pericyte loss in the early stages of diabetic retinopathy using streptozotocin (STZ)-induced mice model of diabetes.
DR mice model was created by injecting STZ (150mg/kg body weight) peritoneally. At four weeks after the STZ injection, the mice were divided into two groups and peritoneally injected aflibercept (25mg/kg) or saline vehicle. After 8 weeks of STZ injection, degree of vascular permeability was measured with fluorescein angiography in live mice. At 4, 6 and 8 weeks after STZ injection, eyeballs were enucleated, flat-mounted and immunostained to measure pericyte count, perfusion and leukocyte recruitment with platelet-derived growth factor receptor beta (PDGFRB), fluorescein isothiocyanate (FITC) and CD45, respectively. VEGF level in each group was measured and quantified. The effect of aflibercept on pericyte survival, perfusion recovery and leukocyte recruitment were also evaluated.
Early DR model was successfully created with STZ injection showing hyper-permeability and hypo-perfusion. Pericytes count was decreased in DR mice compared to the control mice (p<0.001). Quantitative measure of VEGF level was also upregulated in DR mice retina (p<0.05). Hypo-perfusion of peripheral retina became evident after 6 weeks of DR induction. Recruited and aggregated leukocytes were increased in the same period and appeared at the border of perfused and nonperfused retina, providing the etiology of peripheral perfusion block. By inhibiting VEGF with aflibercept, leukocyte recruitment, aggregation and perfusion block was decreased, and eventually, pericyte loss was attenuated.
Aflibercept could attenuate pericyte loss in STZ-induced DR mice. This leads aflibercept could mitigate early pathology of DR such as hyper-permeability and hypo-perfusion. With these finding, management of early stage of DR could be further evaluated and considered with anti-VEGF treatment.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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