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Jae Chan Kim, Kyoung Woo Kim, Soo Jin Lee, Min-Gyu Choi; Ribonuclease 5 Facilitates Mitosis-driven Corneal Endothelial Wound Healing Via Activation of PI3-kinase/Akt Pathway. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1367.
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© ARVO (1962-2015); The Authors (2016-present)
Ribonuclease (RNase) 5 is known to exert diverse intracellular mechanisms via its nuclear translocation. We investigated the effect of RNase 5 on the corneal endothelial cell (CEC) proliferation, thus the enhancement of corneal endothelial wound healing.
Corneal endothelial wound healing with RNase 5 was evaluated in in vitro human cultured CECs and in in vivo cryo-damaged rabbit models. The alteration of localization of RNase 5 in human CECs by exogenous treatment of RNase 5 was visualized with fluorescence. Then, to reveal the mode of action of RNase 5 in CECs, (p-)Akt, (p-)p27Kip1, cyclin D1, D3 and E expressions were analyzed. The Ki-67 and 5-bromo-2'-deoxyuridine (BrdU) expressions were identified and the cell density analysis was performed to reveal the RNase 5-elicited proliferation of CECs.
RNase 5 up-regulated the survival of CECs and accelerated corneal endothelial wound healing in in vitro and in vivo models. RNase 5 treatment rapidly induced accumulation of cytoplasmic RNase 5 into the nucleus and activated PI3-kinase/Akt pathway in human CECs. Moreover, inhibition of nuclear translocation of RNase 5 reversed RNase 5-induced Akt activation. RNase 5 suppressed p27 and up-regulated cyclin D1, D3 and E by activating PI3-kinase/Akt in CECs to initiate cell cycle progression. Furthermore, RNase 5 treatment increased Ki-67-expressing and BrdU-incorporated proliferating CECs and up-regulated the growth of human cultured CECs.
RNase 5 facilitates mitosis-driven corneal endothelial wound healing via PI3-kinase/Akt activation in CECs. RNase 5 may provide a mechanism to restore the injured corneal endothelium and is thus a useful target for therapeutic exploitation.
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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