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Kim, Eun Chul,Toyono, Tetsuya,Berlinicke, Cynthia A.,Zack, Donald J.,Jurkunas, Ula,Usui, Tomohiko,Jun, Albert S. Association for Research in Vision and Ophthalmolo 2017 Investigative Ophthalmology & Visual Science Vol.58 No.2
<P><B>Purpose</B></P><P>To screen for and characterize compounds that protect corneal endothelial cells against unfolded protein response (UPR) and oxidative stress.</P><P><B>Methods</B></P><P>Bovine corneal endothelial cells (BCECs) were treated for 48 hours with 640 compounds from a Food and Drug Administration (FDA)-approved drug library and then challenged with thapsigargin or H<SUB>2</SUB>O<SUB>2</SUB> to induce UPR or oxidative stress, respectively. Cell viability was measured using the CellTiter-Glo survival assay. Selected “hits” were subjected to further dose-response testing, and their ability to modulate expression of UPR and oxidative stress markers was assessed by RT-PCR, Western blot, and measurement of protein carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) adducts in immortalized human corneal endothelial cells (iHCECs).</P><P><B>Results</B></P><P>Forty-one drugs at 20 μM and 55 drugs at 100 μM increased survival of H<SUB>2</SUB>O<SUB>2</SUB>-challenged cells, and 8 drugs at 20 μM and 2 drugs at 100 μM increased survival of thapsigargin-challenged cells, compared with untreated control cells. Nicergoline, ergothioneine, nimesulide, oxotremorine, and mefenamic acid increased survival of both H<SUB>2</SUB>O<SUB>2</SUB>- and thapsigargin-challenged cells. Oxotremorine altered DNA damage inducible 3 (<I>CHOP</I>) gene expression, glucose-regulated protein 78 kDa (GRP78) and activating transcription factor 4 (ATF4) protein expression, and protein carbonyl and 8-OHdG levels. Mefenamic acid altered GRP78 protein expression and protein carbonyl and 8-OHdG levels.</P><P><B>Conclusions</B></P><P>Oxotremorine and mefenamic acid are potential survival factors for corneal endothelial cells under UPR and oxidative stress. The described assay can be further expanded to screen additional drugs for potential therapeutic effect in corneal endothelial diseases such as Fuchs' endothelial corneal dystrophy.</P>
Hong, Soyoung,Yun, Je Hwan,Kim, Eun-Soon,Kim, Ji Seon,Tchah, Hungwon,Hwang, Changmo Association for Research in Vision and Ophthalmolo 2018 Investigative ophthalmology & visual science Vol.59 No.3
<P>CONCLUSIONS. We developed a coculture system using a human feeder cell layer and PLGA membrane-based transwell inserts to create human conjunctival epithelial sheets. This system represents a promising strategy to regenerate corneal epithelium by transplantation.</P>
Lee, Hyungwoo,Jang, Hyoik,Choi, Youn A,Kim, Hyung Chan,Chung, Hyewon Association for Research in Vision and Ophthalmolo 2018 Investigative ophthalmology & visual science Vol.59 No.2
<P>CONCLUSIONS. DME patients with diffuse edema exhibit higher sCD14 levels in the AH and more HF in the inner retina than patients with focal edema, indicating severe inflammation. The strong correlation between sCD14 and HF in the inner retina suggests that the HF observed on SD-OCT may be due to activated microglia in DME.</P>