Extreme corneal fragility and thinning, which have a high risk of catastrophic spontaneous rupture, are the cardinal features of brittle cornea syndrome (BCS), an autosomal-recessive generalized connective tissue disorder. Enucleation is frequently the only management option for this condition, resulting in blindness and psychosocial distress. Even when the cornea remains grossly intact, visual function could also be impaired by a high degree of myopia and keratoconus. Deafness is another common feature and results in combined sensory deprivation. Using autozygosity mapping, we identified mutations in PRDM5 in families with BCS. We demonstrate that regulation of expression of extracellular matrix components, particularly fibrillar collagens, by PRDM5 is a key molecular mechanism that underlies corneal fragility in BCS and controls normal corneal development and maintenance. ZNF469, encoding a zinc finger protein of hitherto undefined function, has been identified as a quantitative trait locus for central corneal thickness, and mutations in this gene have been demonstrated in Tunisian Jewish and Palestinian kindreds with BCS. We show that ZNF469 and PRDM5, two genes that when mutated cause BCS, participate in the same regulatory pathway.
The current study confirms the application of CM for assessing morphologic alterations to the epithelium, Bowman's layer, and stroma in keratoconus. Many of the tissue changes observed with CM could be reconciled with observations made using LM. This work provides a framework against which tissue changes in keratoconus can be studied in a clinical context in vivo using CM.
Presumptive centrifugal spread of PrP(Sc) from the brain through the optic nerve occurs in two major types of CJD. PrP(Sc) is a marker of CJD infectivity. Given that routine decontamination may not remove PrP(Sc) from surgical instruments, a careful risk assessment should be made of possible iatrogenic spread of sporadic and variant CJD after surgery to the retina or optic nerve.
We present 7 cases of canalicular involvement with Actinomyces collected over a 5-year period. All patients had involvement of one canaliculus, upper or lower, with lacrimal drainage patent to syringing. Curettings obtained by incising the involved canaliculi yielded Actinomyces species (5 cases) and Arachnia propionica (2 cases), typically in association with a mixed bacterial growth. Our results show that these patients often remain undiagnosed for months or even years, and are treated inappropriately for their recurrent symptoms. Despite sensitivity of Actinomyces to a broad spectrum of antibiotics, medical therapy alone does not eradicate the disease, and surgical evacuation of all concretions is essential to achieve a cure.
Aim: To localise the recently discovered glycoprotein opticin in the adult human eye. Methods: Polyclonal rabbit antisera were raised against two different opticin peptides. Isolated human vitreous collagen fibrils were extracted with 8 M urea and the extract analysed by SDS-PAGE and western blotting. Paraffin embedded sections from two normal eyes were subjected to immunohistochemical analysis. Results: Western blot analysis of the vitreous collagen fibril extract specifically identified opticin as a 45-50 kDa component that migrated as a doublet. Opticin was especially immunolocalised to the vitreous humour where labelling was most intense in the basal and cortical vitreous gel and less intense in the central vitreous. In addition, specific staining was observed along the surfaces of adjacent basement membranes including the internal limiting membrane (ILM) and posterior capsule of the lens. In one eye, labelling was also observed on the anterior lens capsule, but no other ocular tissues were specifically labelled. A type XVIII collagen/endostatin antibody labelled several ocular tissues including the ILM and basal vitreous gel. Conclusion: The immunolocalisation of opticin was confined to the vitreous humour, ILM, and lens capsule. In situ hybridisation studies have previously demonstrated opticin expression by the posterior nonpigmented ciliary epithelium. Thus, the immunolocalisation data support the proposition that the nonpigmented ciliary epithelium secretes opticin into the vitreous cavity where it associates with vitreous collagen and adjacent basement membranes. The staining along the ILM suggests a role for opticin in vitreoretinal adhesion and the co-localisation of opticin with type XVIII collagen/endostatin at the ILM raises the possibility that interactions between these two molecules might contribute to vitreoretinal adhesion.
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