Protective effect of leukemia inhibitory factor on the retinal injury induced by acute ocular hypertension in rats

Jiexuan Lv; Ruxin Gao; Yao Wang; Changquan Huang; Renyi Wu

doi:10.3892/etm.2022.11717

Protective effect of leukemia inhibitory factor on the retinal injury induced by acute ocular hypertension in rats

Exp Ther Med. 2022 Nov 22;25(1):19. doi: 10.3892/etm.2022.11717. eCollection 2023 Jan.

Authors

Jiexuan Lv¹, Ruxin Gao¹, Yao Wang², Changquan Huang^{1

3}, Renyi Wu^{1

3

4}

Affiliations

¹ Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361001, P.R. China.
² Shaanxi Provincial Key Laboratory of Ophthalmology, Shaanxi Institute of Ophthalmology, Shaanxi Clinical Study Center for Ocular Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Medical School, Northwest University, Xi'an, Shaanxi 710002, P.R. China.
³ Fujian Provincial Key Laboratory of Corneal and Ocular Surface Diseases, Xiamen, Fujian 361001, P.R. China.
⁴ Department of Glaucoma, Shanghai Peace Eye Hospital, Shanghai 200437, P.R. China.

Abstract

Glaucoma is one of the leading causes of irreversible blindness worldwide. As such, neuroprotective therapy is essential for the treatment of this disease. Leukemia inhibitory factor (LIF) is a member of the IL-6 cytokine family and the LIF signaling pathway is considered to be one of the major endogenous factors mediating neuroprotection in the retina. Therefore, the present study aimed to investigate the possible effects of LIF in acute ocular hypertension (AOH). The intraocular pressure in rat eyes was raised to 110 mmHg for 1 h by infusing the anterior chamber with normal saline to establish the AOH model. In the treatment group, LIF was then injected into the vitreous cavity after AOH was ceased. The retinal tissues were obtained after the termination of AOH, and H&E staining was conducted to assess the morphological damage. The number of retinal ganglion cells (RGCs) was counted using the Fluoro-Gold retrograde staining method. TUNEL staining was used to determine the extent of apoptosis among the retinal cells. In addition, the protein expression levels of cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), STAT3 and components of the AKT/mTOR/70-kDa ribosomal protein S6 kinase (p70S6K) signaling pathway were examined by western blotting. The results showed that AOH induced tissue swelling and structural damage in the retina, which were reversed by LIF injection. In the LIF treatment group, RGC loss was significantly inhibited and the quantity of TUNEL-stained cells was also significantly reduced, whereas the expression of cleaved caspase-3 and PARP was decreased. Furthermore, increased phosphorylation of STAT3, AKT, mTOR and p70S6K was observed after LIF treatment. By contrast, pretreatment with the STAT3 inhibitor C188-9 or the PI3K/AKT/mTOR inhibitor LY3023414 reversed the LIF-induced inhibition of RGC loss. These results suggested that exogenous LIF treatment inhibited the retinal damage induced by AOH, which was associated with the activation of STAT3 and mTOR/p70S6K signaling. Therefore, LIF may serve a role in neuroprotection for glaucoma treatment.

Keywords: acute ocular hypertension; glaucoma; leukemia inhibitory factor; retinal ganglion cell.

Grants and funding

Funding: The present study was funded by The National Natural Science Foundation of China (grant no. 81570844), The Natural Science Foundation of Fujian Province (grant no. 2011D001), The Medical Innovation Program of Fujian Province (grant no. 2011-CXB-47), The Huaxia Translational Medicine Youth Foundation (grant no. 2017-A-00301) and The Xiamen Science and Technology Program Guiding Project (grant no. 3502Z20189033).