Heterozygosity for SLC4A11 mutations in the parents of children with autosomal recessive CHED appears to be a risk factor for the development of FECD in these cases.
Loss of SLC4A11 activity induces oxidative stress and cell death, resulting in Congenital Hereditary Endothelial Dystrophy (CHED) with corneal edema and vision loss.
To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11-/- mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy.
In conclusion, our data suggests a possible role of SLC4A11 in regulating oxidative stress, and might be responsible for both the etiology and treatment of corneal endothelial dystrophy.
CHED can be divided into 2 types by the modes of inheritance; CHED type 1 (CHED1) with autosomal dominant inheritance and CHED type 2 (CHED2) with autosomal recessive inheritance.
Future studies of the consequences of SLC4A11 dysfunction as well as further understanding of corneal endothelial ion transport will help clarify the involvement of SLC4A11 in the pathophysiology of CHED.
Mutations in SLC4A11 have been associated with 2 different forms of corneal endothelial dystrophy that lead to degeneration of the corneal endothelium, causing opacity of the cornea and gradual vision loss.
Homozygous mutations in SLC4A11 cause 2 rare recessive conditions: congenital hereditary endothelial dystrophy (CHED), affecting the cornea alone, and Harboyan syndrome consisting of corneal dystrophy and sensorineural hearing loss.
Our observations suggest that CHED caused by homozygous SLC4A11 mutations progresses to Harboyan syndrome, but the severity of this may vary considerably.
These results suggest that heterozygous mutations in SLC4A11 are modest contributors to the pathogenesis of adult FCD, suggesting a causality continuum between FCD and CHED.
A novel SLC4A11 mutation (Thr271Met) is associated with autosomal recessive CHED in a pedigree from the Kingdom of Saudi Arabia and provides additional support that mutations in this gene cause disease.