TY - JOUR
T1 - Assessment of differential intraocular pressure response to dexamethasone treatment in perfusion cultured Indian cadaveric eyes
AU - Haribalaganesh , Ravinarayanan
AU - Gowri Priya, Chidambaranathan
AU - Sharmila, Rajendrababu
AU - Krishnadas, Subbaiah
AU - Muthukkaruppan, Veerappan
AU - Willoughby, Colin
AU - Senthilkumari, Srinivasan
N1 - Funding Information:
This study was supported by the Department of Biotechnology (DBT)-Wellcome Trust/India Alliance fellowship ([Grant Number: IA/I/16/2/502694] awarded to Dr. Senthilkumari Srinivasan). The authors acknowledge the Rotary Aravind International Eye Bank, Aravind Eye Hospital, Madurai, India for providing human donor eyes for this study. The authors would like to acknowledge Mr. Mohammad Sithiq, Bio-statistician, AEH, Madurai for his assistance in performing statistical analysis.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/12
Y1 - 2021/1/12
N2 - The purpose of the present study was to assess the differential intraocular pressure response (IOP) to dexamethasone (DEX) treatment at two dose levels (100 or 500 nM) in perfusion cultured Indian cadaveric eyes to investigate glucocorticoid (GC) responsiveness. In a human organ-cultured anterior segment (HOCAS) set-up, the eye pressure was monitored for every 24 h post DEX infusion (100 or 500 nM) or 0.1% ethanol treatment for 7 days after baseline stabilization. The expression of DEX-inducible proteins such as myocilin and fibronectin in HOCAS-TM tissues was assessed by immunostaining. Elevated IOP was observed in 6/16 eyes [Mean ± SEM (mΔIOP): 15.50 ± 1.96 mmHg; 37.5% responders] and 3/15 eyes (Mean ± SEM mΔIOP: 10 ± 0.84 mmHg; 20% responders) in 100 nM and 500 nM dose groups respectively. Elevated IOP in GC responder eyes was substantiated with a significant increase in myocilin (11.8-fold; p = 0.0002) and fibronectin (eightfold; p = 0.04) expression as compared to vehicle-treated eyes by immunofluorescence analysis. This is the first study reporting the GC responsiveness in Indian cadaveric eyes. The observed GC response rate was comparable with the previous studies and hence, this model will enable us to investigate the relationship between differential gene expression and individual GC responsiveness in our population.
AB - The purpose of the present study was to assess the differential intraocular pressure response (IOP) to dexamethasone (DEX) treatment at two dose levels (100 or 500 nM) in perfusion cultured Indian cadaveric eyes to investigate glucocorticoid (GC) responsiveness. In a human organ-cultured anterior segment (HOCAS) set-up, the eye pressure was monitored for every 24 h post DEX infusion (100 or 500 nM) or 0.1% ethanol treatment for 7 days after baseline stabilization. The expression of DEX-inducible proteins such as myocilin and fibronectin in HOCAS-TM tissues was assessed by immunostaining. Elevated IOP was observed in 6/16 eyes [Mean ± SEM (mΔIOP): 15.50 ± 1.96 mmHg; 37.5% responders] and 3/15 eyes (Mean ± SEM mΔIOP: 10 ± 0.84 mmHg; 20% responders) in 100 nM and 500 nM dose groups respectively. Elevated IOP in GC responder eyes was substantiated with a significant increase in myocilin (11.8-fold; p = 0.0002) and fibronectin (eightfold; p = 0.04) expression as compared to vehicle-treated eyes by immunofluorescence analysis. This is the first study reporting the GC responsiveness in Indian cadaveric eyes. The observed GC response rate was comparable with the previous studies and hence, this model will enable us to investigate the relationship between differential gene expression and individual GC responsiveness in our population.
UR - http://www.scopus.com/inward/record.url?scp=85099343672&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-80112-8
DO - 10.1038/s41598-020-80112-8
M3 - Article
C2 - 33436790
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 605
ER -