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Mohammed Rigi, Hyeck-Soo Son, Albert S Jun, Charles Eberhart, Uri Soiberman; Keratoconic eyes have reduced collagen XII in Bowman’s layer. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2414 – A0217.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal biomechanical failure is the hallmark of keratoconus, a common corneal ectasia, however the cause of this failure remains elusive. Collagen type XII (COL12A1), which localizes to Bowman’s layer (BL), is thought to interact with collagen type I and function in stress bearing areas, such as BL. A recent genome-wide association study of keratoconus patients has identified a unique missense mutation in COL12A1. Similarly, proteomic, transcriptomic and immunihistochemical studies of COL12A1 in keratoconus suggest reduced expression at the level of the corneal epithelium and its basement membrane. This study aims to better characterize collagen XII expression in keratoconus corneas compared to non-keratoconus controls.
Full-thickness corneas obtained from 61 keratoconus cases during keratoplasty and 18 non-keratoconus autopsy were used. Tissue microarrays were constructed from corneal keratoconus and non-keratoconus cases and stained with an antibody to collagen XII alpha 1 (Novus Biologicals, Centennial, CO) at a 1:50 dilution. Four skilled observers (MR, HSS, CGE, USS) analyzed collagen XII stained samples and scores were reached by consensus. Corneal epithelium and stroma were evaluated for extent (in percentages by decile; i.e. 0%, 10%, 20%) and intensity (0-3) of staining, with an overall score obtained by multiplying the two. The epithelial basement membrane (BM) and Bowman’s layer were scored for intensity (0-3) of staining alone. A two-tailed Mann-Whitney test was used to compare keratoconus staining scores to controls and a p-value≤0.05 was considered statistically significant.
Median (and interquartile range) staining score in BL was 1 (0.25-1) in controls and 0 (0-0) in keratoconus (p<0.0001). Median BM staining score was 2 (1-2.75) in controls and 0 (0-1) in keratoconus (p<0.0001). Median epithelial staining score was 1.2 (0.7-2.1) in controls and 0.8 (0.2-1.4) in keratoconus (p<0.06). Finally, median stromal staining score was 0.8 (0.75-1.6) in controls and 0.1 (0.1-0.3) in keratoconus (p<0.0001).
Collagen type XII expression is reduced in BL, corneal BM and stroma in keratoconus. This loss of expression suggests a role in the pathogenesis of keratoconus, given the putative protective role of collagen XII in stress bearing areas. Further studies are necessary to investigate the mechanisms that lead to collagen type XII dysregulation in keratoconus.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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