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Ruihua Jing, Bo Ma, Jie Liu, Cheng Pei; CTGF Contributes to the Development of Posterior Capsule Opacification: an in vitro and in vivo study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5632.
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© ARVO (1962-2015); The Authors (2016-present)
The effects of Connective tissue growth factor (CTGF) on the development of posterior capsule opacification (PCO) were investigated both in vitro and in vivo.
In the pig capsular bag model, immunofluorescence was performed to determine expression of epithelialto-mesenchymal transition (EMT) markers. After induced with 60μg/l CTGF for different times, the expressions of p-ERK, t-ERK, p-p38, t-p38, p-JNK and JNK1/2 proteins were detected with Western-blot in HLECs. The expressions of α-SMA, Fn and COL-1 in HLECs induced by 60μg/l CTGF for 24h were detected by Real-time PCR and Western-blot after blocking ERK’s signaling pathway by U0126, and a scratch assay was used to determine cell migration. To build the rat PCO model, blocking the expression of CTGF by shRNA with AAV (adeno-associated virus) vector was injected into the anterior chamber. PCO was observed under slit lamp and the expression of CTGF and α-smooth muscle actin(α-SMA) in posterior capsule were tested with immunohistochemical.
CTGF promoted EMT, proliferation, migration and the expression of p-ERK1/2 protein in LECs but exerted little effect on the expression of p-p38 and p-JNK1/2 proteins. MEK inhibitor U0126 effectively restrained the CTGF-induced expression of α-smooth muscle actin (α-SMA), fibronectin (Fn) and type I collagen (COL-1) in HLECs. CTGF knockdown effectively postponed the onset of PCO in the rats and significantly reduced the expression of α-SMA in the capsule.
CTGF contributed to the development of PCO presumably by promoting proliferation, migration of LECs, EMT and ECM synthesis in HLECs, which is dependent on ERK signalling. Furthermore, blocking CTGF effectively inhibited PCO in the rats and the EMT in the lens capsule.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Fig. 1 Comparison of PCO scores by EPCO software. PCO grades and scores were statistic by EPCO software in each group. The Significant differences were observed in PCO scores compared with the three intracameral injections of the CTGF.shRNA group, * p<0.005, ** p<0.001.
Fig. 2 Effects of the CTGF treatment on the ERK, p38 and JNK signalling pathways. HLECs were treated with 60 μg/l CTGF for different durations. A: Expression of p-ERK1/2, ERK1/2, p-p38, p38, p-JNK1/2 and JNK1/2 proteins detected by Western blot; B: Quantitation of the p-ERK levels as shown in A (* p<0.05 or ** p<0.001); C and D: Quantitation of the p-p38 and p-JNK levels as shown in A.
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