Expresssion Of Leukemia Inhibitory Factor In The Rat Retina Of Acute And Chronic Glaucoma Models

Purpose To investigate the expression of leukemia inhibitory factor (LIF) and its downstream signaling pathways in the rat retina of experimental glaucoma model.Methods1.The acute ocular hypertension was established by infusing the anterior chamber with normal saline and the intraocular pressure(IOP) was elevated to110mmHg for an hour. The retinal tissues were obtained at12h,24h,2d,3d and7d after the ocular hypertension was ceased.2.Chronic ocular hypertension was induced by episcleral vein cautery. The retinal tissues were obtained at3d,1w,2w,3w and4w after chronic ocular hypertension was ceased.Hematoxylin and eosin (H&E) and TUNEL staining were conducted to assess the morphological change and the apoptosis of retinal cells, respectively. Transmission electron microscope was used to determine the presence of apoptic cells in the retina. The expression of LIF, LIF receptor (LIFR), STAT3, phosphorylated STAT3(P-STAT3), Akt, phosphorylated-Akt (P-Akt), ERK, phosphorylated ERK (P-ERK) was determined at different time points after ocular hypertension by western blot analysis. Quantitative real-time PCR was conducted to detect the expression of LIF and LIFR mRNA.Results1.At12h,24h,2d,3d and7d of reperfusion, the thickness of the inner nuclear layer and the inner plexiform layer was decreased and the cell arrangement of retinal ganglion cells (RGCs) and INL was irregular with a significant reduction in the RGC counting. Late apoptosis phenomenon characterized by chromatin condensation and margination, mitochondrial vacuolization and swellingoccurred at12h and3d after acute ocular hypertension. Both the expression of LIF protein and mRNA were increased after acute ocular hypertension and reached the highest level at12h after retinal reperfusion. The LIFR protein and mRNA levels were both upregulated and peaked at3d after retinal reperfusion. At12h after retinal reperfusion, the levels of P-STAT3and P-Akt were significantly higher than in the normal retina, while P-ERK was detected to be reduced since12h after the retinal reperfusion in the rat retina.2.The thickness of the inner nuclear layer and the outer plexiform layer was decreased and the nucleus of (RGCs) were in different size with a significant reduction in the RGC counting. The thickness of retinal nerve fiber layer was significantly decreased at4w after chronic ocular hypertension compared with the normal retina. The number of apoptosis cells were significantly increased after chronic ocular hypertension compared with normal retina. Both the expression of LIF protein and mRNA were increased after chronic ocular hypertension. The expression of LIF protein reached the highest level at2w after chronic ocular hypertension while the level of LIF mRNA reached the highest at3d after chronic ocular hypertension. The LIFR protein and mRNA levels were both upregulated and peaked at4w after chronic ocular hypertension. At3d after chronic ocular hypertension, the levels of P-STAT3and P-Akt were significantly higher than in the normal retina.The expression of P-ERK was detected to be reduced in the rat retinaat3d、1w、3w、4w after chronic ocular hypertension,while the expression of P-ERK at2w after chronic ocular hypertension has no signigicantly difference with the normal retina.Conclusion The change in the expression of LIF and LIFR after ocular hypertension suggests that LIF may probably play an important role in the process of retinal degeneration/protection induced by experimental galucoma via the activation of JAK-STAT3and Akt signaling pathways.