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Corneal Epithelial Abrasion with Ocular Burr As a Model for Cornea Wound Healing
Published on: July 10, 2018
Central Corneal Epithelial Wounding Accelerates Aniridia-Associated Keratopathy in PAX6-Deficient Mice
Yedizza Rautavaara1, Israa Sefawi1, Meri Vattulainen1
1Division of Ophthalmology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Purpose:
To investigate corneal healing in a Pax6+/- mouse model of aniridia-associated keratopathy (AAK) when challenged with a mild epithelial wound.
Methods:
Pax6+/- small-eye (Sey) mice (n = 15) and Pax6+/+ wild-type mice (n = 4) on the 129S1/SvImJ background underwent 1 mm central corneal mechanical epithelial debridement. Corneal status before and four weeks after wounding was evaluated by slit-lamp imaging. Longitudinal corneal thickness was measured using optical coherence tomography (OCT), and AAK was graded in Sey mice. Wounded corneas were additionally compared to unwounded contralateral corneas for AAK status. Immunofluorescence staining was used to assess inflammation, wound healing, and the presence of corneal blood and lymphatic vessels.
Results:
In wild-type mice, the central epithelial wound healed normally. In contrast, wounded corneas in Sey mice exhibited significantly accelerated AAK progression at 4 weeks compared to unwounded contralateral corneas (P = 0.011), with a corresponding increase in mean AAK grade relative to pre-wounding levels (P = 0.001). AAK grade correlated positively with increased central corneal thickness in wounded (P = 0.031) and unwounded (P = 0.0006) Sey mice. Wounded corneas in Sey mice exhibited strong hemangiogenesis and lymphangiogenesis and altered epithelial phenotype with decreased CK12 and elevated MUC5AC expression, along with an increase in F4/80, IL-6, and IL-1β inflammation markers. Aberrant epithelial differentiation and stem/progenitor maintenance (CK15, SOX9), and persistent tissue repair (Ki-67) were present and were consistent with disease progression.
Conclusions:
Central epithelial wounding accelerates AAK progression in Sey mice, highlighting the epithelial fragility in Pax6-aniridia and providing an efficient and robust accelerated model of AAK progression for preclinical studies.
Insights
Corneal wounding worsens aniridia-associated keratopathy (AAK) in Pax6+/- mice, accelerating disease progression. This study establishes an efficient model for AAK research.
Area of Science:
- Ophthalmology
- Genetics
- Developmental Biology
Background:
- Aniridia-associated keratopathy (AAK) is a severe complication of aniridia, often linked to Pax6 gene mutations.
- The corneal epithelium's role and healing capacity in Pax6-deficient models are not fully understood.
Purpose of the Study:
- To investigate corneal healing and AAK progression in a Pax6+/- mouse model following a mild epithelial wound.
- To establish an accelerated preclinical model for AAK.
Main Methods:
- Pax6+/- (Sey) and wild-type mice underwent central corneal epithelial debridement.
- Corneal status, thickness (OCT), and AAK grading were assessed before and 4 weeks post-wounding.
- Immunofluorescence evaluated inflammation, healing, and neovascularization.
Main Results:
- Wounding accelerated AAK progression in Sey mice compared to unwounded controls.
- AAK grade correlated with increased corneal thickness in Sey mice.
- Wounded corneas showed increased hemangiogenesis, lymphangiogenesis, inflammation, and altered epithelial markers.
Conclusions:
- Epithelial wounding exacerbates AAK in Pax6+/- mice, indicating epithelial fragility.
- This model efficiently accelerates AAK progression for preclinical studies.
