Topical Rho-Associated Kinase Inhibitor, Y27632, Accelerates Corneal Endothelial Regeneration in a Canine Cryoinjury Model

Hidetaka Miyagi, Soohyun Kim, Jennifer Li, Christopher J Murphy, Sara M Thomasy

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)352-359
Number of pages8
JournalCornea
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2019

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rho-Associated Kinases
Canidae
Regeneration
Endothelial Cells
Optical Coherence Tomography
Primates
Freezing
Confocal Microscopy
Wound Healing
Cell Count
Dogs
Rabbits
Corneal Edema
Animal Models
Y 27632

ASJC Scopus subject areas

  • Ophthalmology

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Topical Rho-Associated Kinase Inhibitor, Y27632, Accelerates Corneal Endothelial Regeneration in a Canine Cryoinjury Model. / Miyagi, Hidetaka; Kim, Soohyun; Li, Jennifer; Murphy, Christopher J; Thomasy, Sara M.

In: Cornea, Vol. 38, No. 3, 01.03.2019, p. 352-359.

Research output: Contribution to journalArticle

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