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ROCK Inhibitor Converts Corneal Endothelial Cells into a Phenotype Capable of Regenerating In Vivo Endothelial Tissue
- Source :
- The American Journal of Pathology. 181:268-277
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal transplantation. We previously reported that the adhesion of corneal endothelial cells (CECs) to a substrate was enhanced by the selective ROCK inhibitor Y-27632. It is hypothesized that the inhibition of ROCK signaling may manipulate cell adhesion properties, thus enabling the transplantation of cultivated CECs as a form of regenerative medicine. In the present study, using a rabbit corneal endothelial dysfunction model, the transplantation of CECs in combination with Y-27632 successfully achieved the recovery of corneal transparency. Complications related to cell injection therapy, such as the abnormal deposition of the injected cells as well as the elevation of intraocular pressure, were not observed. Reconstructed corneal endothelium with Y-27632 exhibited a monolayer hexagonal cell shape with a normal expression of function-related markers, such as ZO-1, and Na(+)/K(+)-ATPase, whereas reconstruction without Y-27632 exhibited a stratified fibroblastic phenotype without the expression of markers. Moreover, transplantation of CECs in primates in the presence of the ROCK inhibitor also achieved the recovery of long-term corneal transparency with a monolayer hexagonal cell phenotype at a high cell density. Taken together, these results suggest that the selective ROCK inhibitor Y-27632 enables cultivated CEC-based therapy and that the modulation of Rho-ROCK signaling activity serves to enhance cell engraftment for cell-based regenerative medicine.
- Subjects :
- Corneal endothelium
genetic structures
Pyridines
medicine.medical_treatment
Cell
Drug Evaluation, Preclinical
Biology
Regenerative medicine
Pathology and Forensic Medicine
Corneal Transplantation
In vivo
Cell Adhesion
medicine
Animals
Regeneration
Enzyme Inhibitors
Endothelial dysfunction
Cell adhesion
Cells, Cultured
Corneal transplantation
rho-Associated Kinases
Endothelium, Corneal
Endothelial Cells
medicine.disease
Amides
Combined Modality Therapy
eye diseases
Cell biology
Transplantation
Macaca fascicularis
Phenotype
medicine.anatomical_structure
Immunology
Rabbits
Corneal Injuries
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 181
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....85d108bebc0ec29a7d633fad389c73e7