» Articles » PMID: 21412281

Anti-apoptotic Gene Therapy Prolongs Survival of Corneal Endothelial Cells During Storage

Overview
Journal Gene Ther
Date 2011 Mar 18
PMID 21412281
Citations 21
Authors
Affiliations
Soon will be listed here.
Abstract

Corneal transplantation is the most common form of grafting performed worldwide. Corneal endothelial cells (EC) form a monolayer in the posterior portion of the cornea and are essential for corneal transparency. EC loss during storage before transplantation is a principal reason for rendering donor tissue unsuitable for transplantation, and apoptosis has been shown to be the major contributor to EC loss during storage and after transplantation. Therefore, the potential use of anti-apoptotic gene therapy to promote both graft storage and graft survival is of major interest. The goal of this study was to transduce human donor corneas in vitro to enhance EC survival during storage conditions used in eye banking. We utilized a lentiviral vector to perform gene transfer of baculoviral p35 or mammalian Bcl-xL to corneal endothelium in different storage conditions utilizing a lentiviral vector. Our results show significantly enhanced survival and prolonged retention of physiological EC morphology in cells expressing either p35 or Bcl-xL. The clinical application of this technology could lead to a higher availability of donor tissue for transplantation, extend storage periods and reduce graft failure after transplantation.

Citing Articles

Suppressing Pro-Apoptotic Proteins by siRNA in Corneal Endothelial Cells Protects against Cell Death.

Staehlke S, Mahajan S, Thieme D, Trosan P, Fuchsluger T Biomedicines. 2024; 12(7).

PMID: 39062012 PMC: 11274739. DOI: 10.3390/biomedicines12071439.


Corneal Regeneration Using Gene Therapy Approaches.

Sarkar S, Panikker P, DSouza S, Shetty R, Mohan R, Ghosh A Cells. 2023; 12(9).

PMID: 37174680 PMC: 10177166. DOI: 10.3390/cells12091280.


Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms.

Chen L, Jiang X, Gao S, Liu X, Gao Y, Kow A Front Pharmacol. 2022; 13:1032069.

PMID: 36386146 PMC: 9663918. DOI: 10.3389/fphar.2022.1032069.


Nanoneedles Induce Targeted siRNA Silencing of p16 in the Human Corneal Endothelium.

Maurizi E, Martella D, Schiroli D, Merra A, Mustfa S, Pellegrini G Adv Sci (Weinh). 2022; 9(33):e2203257.

PMID: 36253148 PMC: 9685449. DOI: 10.1002/advs.202203257.


Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review.

Smeringaiova I, Utheim T, Jirsova K Stem Cell Res Ther. 2021; 12(1):554.

PMID: 34717745 PMC: 8556978. DOI: 10.1186/s13287-021-02611-3.


References
1.
Vasara K, SETALA K, Ruusuvaara P . Follow-up study of human corneal endothelial cells, photographed in vivo before enucleation and 20 years later in grafts. Acta Ophthalmol Scand. 1999; 77(3):273-6. DOI: 10.1034/j.1600-0420.1999.770305.x. View

2.
Beutelspacher S, Ardjomand N, Tan P, Patton G, Larkin D, George A . Comparison of HIV-1 and EIAV-based lentiviral vectors in corneal transduction. Exp Eye Res. 2005; 80(6):787-94. DOI: 10.1016/j.exer.2004.12.005. View

3.
Sattler M, Liang H, Nettesheim D, Meadows R, Harlan J, Eberstadt M . Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science. 1997; 275(5302):983-6. DOI: 10.1126/science.275.5302.983. View

4.
Garg P, Krishna P, Stratis A, Gopinathan U . The value of corneal transplantation in reducing blindness. Eye (Lond). 2005; 19(10):1106-14. DOI: 10.1038/sj.eye.6701968. View

5.
Crewe J, Armitage W . Integrity of epithelium and endothelium in organ-cultured human corneas. Invest Ophthalmol Vis Sci. 2001; 42(8):1757-61. View