title: Development of a novel in vivo corneal fibrosis model in the dog.
abstract: The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading scale, modified McDonald-Shadduck (mMS) scoring system, optical coherence tomography (OCT), corneal histopathology, immunohistochemistry (IHC), and transmission electron microscopy (TEM). The used alkali burn dose to produce corneal fibrosis was well tolerated as no significant difference in mMS scores between control and treatment groups (p = 0.89) were detected. The corneas of alkali burned dogs showed significantly greater levels of α-smooth muscle actin, the fibrotic marker, than the controls (p = 0.018). Total corneal thickness of all dogs post-burn was significantly greater than baseline OCT images irrespective of treatment (p = 0.004); TEM showed that alkali burned corneas had significantly greater minimum and maximum interfibrillar distances than the controls (p = 0.026, p = 0.018). The tested topical corneal alkali burn dose generated significant opacity and fibrosis in dog corneas without damaging the limbus as evidenced by histopathology, IHC, TEM, and OCT findings, and represents a viable large animal corneal fibrosis in vivo model. Additional in vivo SAHA dosing studies with larger sample size are warranted.
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, Columbia, MO, USA; Harry S. Truman Memorial Veteran Hospital, Columbia, MO, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Gronkiewicz
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, Columbia, MO, USA; Harry S. Truman Memorial Veteran Hospital, Columbia, MO, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Giuliano
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, Columbia, MO, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Department of Computer Science, University of Missouri, Columbia, MO, USA.
authors.forename: F
authors.initials: F
authors.lastname: Bunyak
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, Columbia, MO, USA; Harry S. Truman Memorial Veteran Hospital, Columbia, MO, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Pathological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA.
authors.forename: L B C
authors.initials: LB
authors.lastname: Teixeira
authors.affiliation: Mason Eye Institute, University of Missouri, Columbia, MO, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, Columbia, MO, USA; Harry S. Truman Memorial Veteran Hospital, Columbia, MO, USA; Mason Eye Institute, University of Missouri, Columbia, MO, USA. Electronic address: mohanr@health.missouri.edu.
authors.forename: R R
authors.initials: RR
authors.lastname: Mohan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002057:Burns, Chemical / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003315:Cornea / Q000378:metabolism / Q000473:pathology*; D003316:Corneal Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004285:Dogs; D005126:Eye Burns / Q000139:chemically induced; D005260:Female; D005355:Fibrosis; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006877:Hydroxamic Acids / Q000627:therapeutic use; D007150:Immunohistochemistry; D012972:Sodium Hydroxide / Q000633:toxicity; D041623:Tomography, Optical Coherence; D000077337:Vorinostat
chemical_list: D000199:Actins; D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012972:Sodium Hydroxide; D000077337:Vorinostat
keywords: Alkali burn; Corneal fibrosis; Dog; Suberanilohydroxamic acid; α-smooth muscle actin