Protective effect of leukemia inhibitory factor on light induced retinal photoreceptors damage and its mechanisms

Abstract

Objective To investigate the role of leukemia inhibitory factor (LIF) on retinal photoreceptor cells and the underlying mechanism after light damage. Methods Fifty 5-6 weeks old BALB/c mice were randomly divided into normal control group (10 mice), light damage+ LIF group (20 mice) and light damage+ PBS group (20 mice). Four days before exposing to light, the right eye of each animal in light damage+ LIF group and light damage+ PBS group was injected with LIF and PBS, respectively; then the mice in the light damage+ LIF group and light damage+ PBS group were exposed to 4 000 lx intensity of cool white fluorescent light for 4 hours to establish the experimental model of retinal light damage.The function and morphology of retinal photoreceptor cells were detected by flash electroretinogram (fERG) and histopathological examination.Real-time PCR was used to detect the mRNA expression of Jak3, STAT3, and apoptosis-related factor Bcl-2 and Bax.The use of animals is guided by the State Science and Technology Commission's regulations on the management of experimental animals. Results The amplitudes of scotopic ERG a wave of 0.01, 1, 100, 200, 400 cd·s/m2 light in the light damage+ PBS group were significantly lower than those in the normal control group and light damage+ LIF group (all at P<0.05). The amplitudes of photopic ERG b wave of different color light in the light damage+ PBS group were significantly lower than those in the normal control group and light damage+ LIF group (all at P<0.05). The number of photoreceptor nuclei in the light damage+ PBS group was significantly lower than that in the normal control group and light damage+ LIF group (both at P<0.05). Compared with light damage+ PBS group, the relative expression of Jak3, STAT3, Bcl-2 mRNA in light damage+ LIF group were significantly increased (all at P<0.05), and the relative expression of Bax mRNA were significantly decreased (P<0.05). Conclusions LIF can protect retinal photoreceptor cells from light damage, which may result from the activation of Jak3/STAT3 signaling pathway and inhibition of its downstream Bax/Bcl-2 apoptotic pathway. Key words: Leukemia inhibitory factor; Photoreceptor; Light damage; Neuroprotection