Abstract
Purpose :
Zika virus (ZIKV), a mosquito-borne flavivirus, can cause severe eye disease characterized by chorioretinal atrophy, optic neuritis, and blindness in newborns. However, the retinal lesion progress has not been described explicitly. Here, we developed an easily manipulated mouse model of ZIKV infection to evaluate its impact on retina.
Methods :
ZIKV (20 PFU) was injected into the neonatal C57BL/6 mice at Postnatal day (P) 0 subcutaneously. Retinas of ZIKV-infected mice and age-matched controls were collected at P5, P8, P11, P14 and P21. Neural injury, vascular damage, inflammation, and gliosis were analyzed by immunostaining with anti-Tuj-1, isolectin B4, anti-CD31, anti-CD45, anti-Iba1 and anti-GFAP in retinal flatmounts. Retinal structural alteration was assessed in retinal sections by PI staining.
Results :
RGC axons began to degenerate in ZIKV group starting at P8, with local abnormal vasculature, slightly increased leukocytes infiltration, and mild activation of astrocytes and microglia. With the passage of time, RGC axons got thinner, and RGC loss and vascular degeneration were more severe, associated with exacerbated leukocyte infiltration and gliosis, especially at P21. Interestingly, retinal thickness was slightly thicker in ZIKV group than control group at P11 because of the deficiency of retinal differentiation influenced by ZIKV. Thereafter, retinal structure was destroyed severely and retinal thickness was remarkably reduced. In addition, retinal size in ZIKV-infected group got smaller than control mice starting at P11.
Conclusions :
We established a novel and easily manipulated mouse model of retinal abnormalities associated with ZIKV and found its devastating consequences during retinal development. The neuronal death, abnormal vasculature, gliosis and structural disorder indicate that ZIKV has impact on the retina starting at around P8 and the infection can lead to a severe influence on the eye.
This is a 2020 ARVO Annual Meeting abstract.