Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 47, Issue 2, Pages 565-573Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.05-0771
Keywords
-
Categories
Ask authors/readers for more resources
PURPOSE. Type V collagen forms heterotypic fibrils with type I collagen and accounts for 10% to 20% of corneal collagen. The purpose of this study was to define the ocular phenotype resulting from mutations in the type V collagen genes COL5A1 and COL5A2 and to study the pathogenesis of anomalies in a Col5a1-deficient mouse. METHODS. Seven patients with classic Ehlers-Danlos syndrome (EDS) due to COL5A1 haploinsufficiency and one with an exon-skipping mutation in COL5A2 underwent an ocular examination, corneal topography, pachymetry, and specular microscopy. A Col5a1-haploinsufficient mouse model of classic EDS was used for biochemical and immunochemical analyses of corneas. Light and electron microscopy were used to quantify stromal thickness, fibril density, fibril structure, and diameter. RESULTS. Five males and three females (mean age, 26 +/- 13.57 years; range, 11 - 52) were studied. All patients had floppy eyelids. The corneas of all eyes were thinner (mean corneal thickness: 435.75 +/- 12.51 mu m) when compared with control corneas (568.89 +/- 28.46 mu m; P < 0.0001). In the Col5a1(+/-) mouse cornea, type V collagen content was reduced by similar to 49%, and stromal thickness was reduced by similar to 26%. Total collagen deposition in Col5a1(+/-) corneas also was reduced. Collagen fibril diameters were increased, but fibril density was decreased throughout the stroma at all developmental stages. CONCLUSIONS. In the eye, COL5A1 and COL5A2 mutations manifest as abnormally thin and steep corneas with floppy eyelids. Mechanisms involved in producing the latter anomalies probably involve altered regulation of collagen fibrillogenesis due to abnormalities in heterotypic type I/V collagen interactions similarto those observed in the Col5a1(+/-) mouse cornea.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available