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.