Microglial density determines the appearance of pathological neovascular tufts in oxygen-induced retinopathy

Wenqin Xu, Zhicha Hu, Yang Lv, Guorui Dou, Zifeng Zhang, Haiyan Wang, Yusheng Wang

The oxygen-induced retinopathy (OIR) animal model established in C57 mice and SD rats has been widely used in retinal neovascular disease studies, while Balb/c mice have not been used because Balb/c OIR mice lack neovascular tufts. One study found a substantial difference in the density of retinal microglia between C57 and Balb/c mice; however, no direct evidence could clarify whether the density of retinal microglia in Balb/c mice led to this difference. In our study, intraperitoneal injection of minocycline was used to inhibit the activation of microglia and intravitreal injection of clodronate liposomes was used to decrease the density of microglia in Balb/c OIR model mice. We found that with the decline in microglia induced by the two drugs, the avascular area in treated Balb/c OIR mice was higher than that in untreated Balb/c OIR mice; moreover, a small area of neovascular tufts appeared at P17. After checking the expression of Iba1, a microglial marker and GFAP, an astrocyte and Müller cell marker, we found that minocycline and clodronate could inhibit the activation of microglia or decrease the density of microglia, while they had no significant effect on astrocytes and Müller cells. Therefore, these data suggest that the density of microglia in the retina may determine the result of vasculopathy in OIR mice to some extent. In future studies, predicting the development of retinal neovascular diseases by detecting the density of microglia in living animals or human beings with newly developed instruments and methods may be useful.