In keratoconus corneas, levels of degradative enzymes, including lysosomal acid phosphatase (LAP) and cathepsin B, are elevated, and those of the inhibitors alpha1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-M) are reduced, especially in the epithelial layer.
The ABCA6 locus (rs77542162) was associated with keratoconus using the TwinsUK (odds ratio [OR], 0.50; 95% CI, 0.27-0.92; P = .03) and EPIC-Norfolk controls (OR, 0.39; 95% CI, 0.22-0.70; P = .002).
Competitive polymerase chain reaction (PCR) was used to determine the messenger RNA (mRNA) levels for lysosomal acid phosphatase and alpha 1-PI in epithelial and stromal cells of keratoconus corneas.
The other loci were associated with keratoconus using TwinsUK (OR per effect allele for ADAMTS8, 0.51 [95% CI, 0.37-0.71; P = 7.9 × 10-5]; for COL6A1, 1.65 [95% CI, 1.05-2.59; P = .03]) or EPIC-Norfolk (OR per effect allele for ANAPC1, 0.78 [95% CI, 0.68-0.89; P = 3.7 × 10-4]; for ADAMTS17, 0.82 [95% CI, 0.68-0.99; P = .04]) controls.
The other loci were associated with keratoconus using TwinsUK (OR per effect allele for ADAMTS8, 0.51 [95% CI, 0.37-0.71; P = 7.9 × 10-5]; for COL6A1, 1.65 [95% CI, 1.05-2.59; P = .03]) or EPIC-Norfolk (OR per effect allele for ANAPC1, 0.78 [95% CI, 0.68-0.89; P = 3.7 × 10-4]; for ADAMTS17, 0.82 [95% CI, 0.68-0.99; P = .04]) controls.
A novel His403Gln variant in transforming growth factor, beta-induced (TGFBI), that may be causing keratoconus was also identified, indicating likely digenic inheritance of keratoconus and ADH2 in this family.
Sixteen patients with genotyped LCA (having the CRB1, CRX, RetGC, RPE65, and AIPL1 mutations) were recruited from one ophthalmology practice and examined for the presence of keratoconus.
The phenotype of LCA in patients with AIPL1 mutations is relatively severe, with a maculopathy in most patients and keratoconus and cataract in a large subset.
Our study highlighted the potential roles of several genes (CTGF, SFRP1, AQP5, lnc-WNT4-2:1, and lnc-ALDH3A2-2:1) and pathways (TGF-β, WNT signaling, and PI3K/AKT pathways) in KC pathogenesis.
Our study highlighted the potential roles of several genes (CTGF, SFRP1, AQP5, lnc-WNT4-2:1, and lnc-ALDH3A2-2:1) and pathways (TGF-β, WNT signaling, and PI3K/AKT pathways) in KC pathogenesis.
The other loci were associated with keratoconus using TwinsUK (OR per effect allele for ADAMTS8, 0.51 [95% CI, 0.37-0.71; P = 7.9 × 10-5]; for COL6A1, 1.65 [95% CI, 1.05-2.59; P = .03]) or EPIC-Norfolk (OR per effect allele for ANAPC1, 0.78 [95% CI, 0.68-0.89; P = 3.7 × 10-4]; for ADAMTS17, 0.82 [95% CI, 0.68-0.99; P = .04]) controls.
The aim of this study was to determine the relationship between the genotypes of the c.444 T>G (rs1130409) and c.-468 T>G (rs1760944) polymorphisms in the APEX1 gene and the occurrence of two oxidative stress-related eye diseases: keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD).
KC6 is a novel gene of unknown function that shows cornea-preferred expression, whereas the suppression of transcripts for AQP5 provides the first clear evidence of a molecular defect identified in KC.
In this prospective population-based cohort study, 5-year changes in Belin grading system indices including the average radii of curvature in the 3 mm zone surrounding the thinnest point in the anterior (ARC-3 mm) and posterior (PRC-3 mm) cornea, corrected distance visual acuity, minimum corneal thickness, maximum Ambrosio's relational thickness (ART-max), and maximum anterior keratometry indices centered on steepest point in the central 3 mm (Kmax-3 mm), 4 mm (Kmax-4 mm), and 5 mm (Kmax-5 mm) zones were compared between keratoconus and normal participants.