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Cheng Pei, Bo Ma, Ruihua Jing; Effects of Gremlin on Posterior Capsular Opacification：An in vitro and in vivo study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1605.
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© ARVO (1962-2015); The Authors (2016-present)
The study aims to investigate the effects of gremlin on the development of posterior capsular opacification (PCO) both in vitro and in vivo.
The role of BMPs/Smad1/5, MAPK, FAK and AKT signaling pathways and their relationships in human lens epithelial cells (HLECs) treated with gremlin were detected by Western-blot and real-time PCR. Wound healing and Transwell assays were used to test the migration ability of gremlin in HLECs. Capsular bag models were established to examine the proliferation and the epithelial mesenchymal transition (EMT) of HLECs after treatment with gremlin. Rat PCO models were established to examine the effects of gremlin knockdown by shRNA adeno-associated virus on PCO development. The immunohistochemical staining was performed to detect the expression of α-smooth muscle actin (α-SMA) in the anterior and posterior capsule in vivo.
We found that gremlin treatment could promote the expression of p-ERK and p-AKT while exerted little effect on p-p38, p-JNK, and p-FAK expression and cell migration in HLECs. Gremlin could effectively reduce the expression of p-Smad1/5 protein after treatment with BMP4, a Smad1/5 signaling activator. In contrast, the treatment of ERK and AKT inhibitors, U0126 and LY294002, could significantly suppress the gremlin-induced expression of α-SMA, Fn and COL-1 in HLECs. We also found that knockout of either Smad2 or Smad3 could effectively inhibit the expression of both p-ERK and p-AKT protein induced by gremlin. Moreover, gremlin knockdown effectively inhibited the development of PCO in rats and significantly reduced the expression of α-SMA in the anterior and posterior capsule.
These results suggested that gremlin contributed to the development of PCO by promoting LECs proliferation, activating TGF-β/Smad, ERK and AKT signalling pathway and inhibiting BMPs/Smad1/5 signalling pathway. Furthermore, inhibiting gremlin effectively impaired both PCO development in a rat and EMT in the lens capsule. These data show that gremlin might be a new promising drug target for the prevention and treatment of PCO.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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