Phenotyping Slc4a11 knock-out mouse model of Congenital Hereditary Endothelial Dystrophy (CHED)

Title Phenotyping Slc4a11 knock-out mouse model of Congenital Hereditary Endothelial Dystrophy (CHED)
Author, Co-Author Wenlin Zhang, Diego Ogando, Joseph Bonanno
Topic Cornea/anterior segment/external/dry eye
Year
2016
Day
Friday
Program Number
165215
Room
Ballroom A-B
Affiliation
Indiana University School of Optometry
Abstract

Purpose: Congenital Hereditary Endothelial Dystrophy (CHED) is characterized by presentation at or soon after birth of diffuse corneal edema with bilateral involvement, and without other significant developmental abnormalities of the anterior segment. CHED can either be progressive or non-progressive. CHED is recognized as an anomalous development of neural crest origin corneal endothelium during or after fifth month of gestation. Histologically, the diffusely edematous corneal stroma accounts for the marked increase in corneal thickness observed clinically. Uniform thickening of Descemet’s membrane and vacuolation of corneal endothelium are characteristic histological findings of CHED. Additionally, marked epithelium thinning with variability of cell layer numbers, focal loss of polarity and intracellular edema especially at the base of epithelium were considered secondary in nature. The genetic loci for CHED has been mapped to 20p13 and SLC4A11 mutations were reported to cause CHED. Since then, 74 mutations in 17 of the 19 coding exons of SLC4A11 have been identified thus far. In this study, we examined homozygous Slc4a11 knock-out (KO) C57BL/6 mice with a targeted deletion of exons 9 to 13 of the murine Slc4a11 gene as a model for CHED.

Method: Mouse cornea edema was monitored by light microscopy and anterior segment optical coherent tomography (AS-OCT, iVue) at 12 weeks and 40 weeks. Histological cornea sections (40 weeks) were stained with hematoxylin and eosin (H&E) and imaged with AxioImager M1 microscope (Zeiss).

Results: Slc4a11 KO mouse recapitulates diffuse corneal edema seen in CHED, with ground glass appearance under light microscopy and with progression monitored longitudinally via AS-OCT. Histologically, edematous corneal stroma, uniformly thickened Descemet’s membrane with increased auto-fluorescence and vacuolated corneal endothelium are all present in Slc4a11 KO mouse cornea. Furthermore, secondary corneal epithelium changes are also present, which include various degrees of epithelium thinning with loss of superficial squamous cells, basal epithelial cell edema and loss of polarity accompanied with focal epithelial hyperplasia.

Conclusion: In summary, Slc4a11 KO C57BL/6 mouse provides a good animal model for CHED.

Affiliation of Co-Authors Indiana University, Indiana University
Outline