A sclerocornea-associated RAD21 variant induces corneal stroma disorganization.

Sclerocornea is a cornea opacification disorder. Disorganized corneal stroma fibrils are observed in patients' cornea. Previously we identified a RAD21C1348T variant that is associated with a peripheral sclerocornea pedigree. To explore whether this RAD21 variant can induce sclerocornea-related phenotype, and to investigate the possible mechanisms of such phenotype, the orthologous rad21 wild-type and variant mRNAs were injected into Xenopus laevis embryos and the developed eyes were subjected for histological examination. Transmission electron microscopy was applied for corneal stroma organization check. rad21 is highly expressed in the eye region during X. laevis development. Disrupted eye development was observed in the rad21 variant injected embryos. Disorganized corneal stroma and decreased diameters of collagen fibrils were observed in the rad21 variant injected X. laevis eyes. These eye defects can be rescued by overexpression of the wild-type rad21. Histological examination found stroma attracting center, a key structure in X. laevis corneal development, was impaired in rad21 variant injected embryos. Our results suggest a key role of RAD21 during corneal development. Our data indicates the RAD21R450C variant contributes to peripheral sclerocornea by disturbing collagen fibril organization in the corneal stroma.

[Molecular genetics of development of cornea].

This paper mainly reviews sources discussed in recent years that are devoted to the genetics of corneal development. Genetically caused separation processes of corneal bud and its specification and differentiation are considered. It is shown that mutation disorders in the genes responsible for differentiation of the cornea can lead to different forms of dystrophies and other corneal disorders.

Anterior segment developmental anomalies in a 33-week-old fetus with MIDAS syndrome.

We report anterior segment abnormalities in both eyes of a 33-week-old fetus endorsing the diagnosis of MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome. After abortion, the fetus was examined by a standard pediatric autopsy that included macroscopic and microscopic examination of both eyes. Postmortem findings included craniofacial stigmata (such as hypertelorism, a flat nose and low-set ears) and an agenesis of the corpus callosum. Array comparative genomic hybridization revealed a deletion of the short arm of the X chromosome (region Xp22.2 to p22.32). Ophthalmopathologic examination of the eyes revealed microphthalmia with anterior segment developmental anomalies, in particular sclerocornea and Peters' anomaly, respectively. General pathology findings plus the ocular findings allowed the diagnosis of MIDAS syndrome. A discussion of differential diagnoses is provided. This case report indicates that ophthalmopathologic investigation of fetal eyes can be of great value for the further classification of syndromes.

In vivo microstructural analysis of the cornea in Scheie's syndrome.

PURPOSE: To analyze clinical and in vivo microstructural characteristics of both corneas of a 13-year-old male subject with Scheie's syndrome and compare the observations with the pathologic reports in the literature. METHODS: Standard clinical examination and real-time, slit-scanning in vivo confocal microscopy were performed and repeated after 1 year. RESULTS: In vivo confocal microscopy images at all cellular layers demonstrated brighter intercellular spaces than those of normal corneas. Cicatrization of the anterior stroma was identified, and the keratocytes of the middle and posterior stroma exhibited markedly altered morphology, often round or elliptical in shape, and with clearly demarcated, hyporeflective centers. The nerve fibers of the subbasal plexus were somewhat more irregular and difficult to distinguish, possibly due to underlying fibrosis. CONCLUSIONS: The potential of in vivo confocal microscopy to highlight microstructural alterations of the intact human cornea and evaluate such changes over time might reduce reliance on histopathologic investigations in such conditions and contribute to the ophthalmic management of the mucopolysaccharidoses in the future.

Axenfeld's anomaly and related disorders.

Axenfeld's anomaly is a bilateral disorder characterized by a prominent, anteriorly displaced. Schwalbe's line (posterior embryotoxon) and peripheral iris strands which span the anterior chamber angle to attach to Schwalbe's line. Although this particular condition is benign, the two clinical features manifested are observed in other ocular disorders with potentially sight-threatening sequelae. An asymptomatic patient with Axenfeld's anomaly presented to our office for routine eye care. A case report, discussion of the condition and differential diagnoses are presented regarding this ocular anomaly and related disorders.

Hereditary sclerocornea.

Sclerocornea is a primary anomaly in which scleralization of a peripheral part of the cornea, or the entire corneal tissue, occurs. In the peripheral type of sclerocornea, the affected area is vascularized with regular arcades of superficial scleral vessels. In total sclerocornea, the entire cornea is opaque and vascularized. To our knowledge, 97 cases of all types of sclerocornea have been reported in the world literature, either as a primary anomaly or in association with cornea plana. Peripheral sclerocornea in association with cornea plana was found in nine members of one family, in four of five generations studied. To our knowledge, this is the largest pedigree of hereditary peripheral sclerocornea identified. Our pedigree suggests the autosomal-dominant transmission of this entity but doesn't rule out phenocopies or other modes of inheritance in other cases of sclerocornea. Chromosomal analyses of representative family members revealed normal karyotypes.

Classification of corneal endothelial disorders based on neural crest origin.

The corneal endothelium is derived from the neural crest. A general classification of disorders of development of the neural crest has been previously presented (Johnston). Disorders of the corneal endothelium may be considered according to a modification of this scheme to reflect its true embryologic origin. In this classification, corneal endothelial disorders are categorized as abnormalities of neural crest cell formation (cyclopia), migration (Peters' anomaly), proliferation (iridocorneal endothelial syndrome), final differentiation (Fuchs' dystrophy), and acquired abnormalities (metaplasia, abiatrophy, and proliferation).