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Topical Rho-Associated Kinase Inhibitor, Y27632, Accelerates Corneal Endothelial Regeneration in a Canine Cryoinjury Model
- Source :
- Cornea. 38:352-359
- Publication Year :
- 2018
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2018.
-
Abstract
- Purpose Corneal endothelial cell regeneration varies by species, with nonhuman primates (NHPs) and rabbits displaying low and high proliferative capacities, respectively. Recent studies report that topical application of rho-associated kinase (ROCK) inhibitors accelerates corneal endothelial wound healing in animal models and human patients with endothelial dysfunction. This study determines the regenerative capacity of canine corneal endothelial cells in vivo and their response to a topical ROCK inhibitor, Y27632, after transcorneal freezing. Methods Right eyes of 6 beagles underwent transcorneal freezing; 10 mM ROCK inhibitor Y27632 or vehicle control was applied topically to both eyes at least 4 times daily for 56 days. Endothelial cell density was evaluated by in vivo confocal microscopy, and corneal thickness was measured by Fourier-domain optical coherence tomography (FD-OCT) and ultrasound pachymetry. Results Transcorneal freezing induced severe central corneal edema in dogs, with restoration of transparency occurring within 4 weeks. Y27632 significantly decreased corneal thickness by FD-OCT and ultrasound pachymetry in the acute phase and significantly increased endothelial cell density at days 28 and 42 post-cryoinjury, suggesting faster restoration of endothelial cell recovery. Conclusions Canine corneal endothelial function recovers at a similar rate as NHPs but more slowly than rabbits after cryoinjury. Faster corneal endothelial wound healing was observed by in vivo confocal microscopy and FD-OCT in dogs treated with Y27632 versus vehicle controls. Thus, a canine cryoinjury model may be a useful alternative to NHPs in detecting a response to therapies directed at endothelial regeneration.
- Subjects :
- Pathology
medicine.medical_specialty
genetic structures
Endothelium
Pyridines
Cell Count
Article
03 medical and health sciences
Dogs
0302 clinical medicine
Decreased corneal thickness
In vivo
medicine
Animals
Endothelial dysfunction
Cold Injury
Protein Kinase Inhibitors
Rho-associated protein kinase
Wound Healing
rho-Associated Kinases
Kinase
business.industry
Regeneration (biology)
Endothelium, Corneal
Endothelial Cells
medicine.disease
Amides
eye diseases
Endothelial stem cell
Disease Models, Animal
Ophthalmology
medicine.anatomical_structure
030221 ophthalmology & optometry
sense organs
business
030217 neurology & neurosurgery
Corneal Injuries
Subjects
Details
- ISSN :
- 02773740
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Cornea
- Accession number :
- edsair.doi.dedup.....cbf1ee7423fb081cc049ad3032e56bf4