Biomedical subjects

Jane L Ashworth

Publications and source records attributed to Jane L Ashworth.

3 recordsLinked to original sources

PubMed2002

Fibrillin: from microfibril assembly to biomechanical function.

Fibrillins form the structural framework of a unique and essential class of extracellular microfibrils that endow dynamic connective tissues with long-range elasticity. Their biological importance is emphasized by the linkage of fibrillin mutations to Marfan syndrome and related connective tissue disorders, which are associated with severe cardiovascular, ocular and skeletal defects. These microfibrils have a complex ultrastructure and it has proved a major challenge both to define their structural organization and to relate it to their biological function. However, new approaches have at last begun to reveal important insights into their molecular assembly, structural organization and biomechanical properties. This paper describes the current understanding of the molecular assembly of fibrillin molecules, the alignment of fibrillin molecules within microfibrils and the unique elastomeric properties of microfibrils.

Animals↗

PubMed2002

Fibrillin-rich microfibrils: elastic biopolymers of the extracellular matrix.

Fibrillin-rich microfibrils are evolutionarily ancient macromolecular assemblies of the extracellular matrix. They have unique extensible properties that endow vascular and other tissues with long-range elasticity. Microfibril extensibility supports the low pressure closed circulations of lower organisms such as crustaceans. In higher vertebrates, microfibrils act as a template for elastin deposition and are components of mature elastic fibres. In man, the importance of microfibrils is highlighted by the linkage of mutations in their principal structural component, fibrillin-1, to the heritable disease Marfan syndrome which is characterised by severe cardiovascular, skeletal and ocular defects. When isolated from tissues, fibrillin-rich microfibrils have a complex ultrastructural organisation with a characteristic 'beads-on-a-strong' appearance. X-ray fibre diffraction studies and biomechanical testing have shown that microfibrils are reversibly extensible at tissue extensions of 100%. Ultrastructural analysis and 3D reconstructions of isolated microfibrils using automated electron tomography have revealed new details of how fibrillin molecules are aligned within microfibrils in untensioned and extended states, and delineated the role of calcium in regulating microfibril beaded periodicity, rest length and molecular organisation. The molecular basis of how fibrillin molecules assemble into microfibrils, the central role of cells in regulating this process, and the identity of other molecules that may coassemble into microfibrils are now being elucidated. This information will enhance our understanding of the elastic mechanism of these unique extracellular matrix polymers, and may lead to new microfibril-based strategies for repairing elastic tissues in ageing and disease.

Animals↗

PubMedDate not supplied

Mucopolysaccharidoses and the eye.

The mucopolysaccharidoses (MPSs) are a group of disorders caused by inherited defects in lysosomal enzymes resulting in widespread intra- and extra-cellular accumulation of glycosaminoglycans. They have been subdivided according to enzyme defect and systemic manifestations and include MPS IH (Hurler), MPS IS (Scheie), MPS IH/S (Hurler/Sheie), MPS II (Hunter), MPS III (Sanfilippo), MPS IV (Morquio), MPS VI (Maroteaux-Lamy), MPS VII (Sly) and MPS IX (Natowicz). The mucopolysaccharidoses have a spectrum of systemic manifestations, including airway and respiratory compromise, skeletal deformities, intellectual and neurological impairment, cardiac abnormalities, and gastrointestinal problems. Ocular manifestations are common in the mucopolysaccharidoses and may result in significant visual impairment. Corneal opacification of varying severity is frequently seen, as well as retinopathy, optic nerve swelling and atrophy, ocular hypertension, and glaucoma. New treatment modalities for the systemic manifestations of the mucopolysaccharidoses include bone marrow transplant and enzyme replacement therapy, and have resulted in an improved prognosis in many cases. This article reviews the systemic and ocular manifestations of the mucopolysaccharidoses, as well as new treatment options, and discusses the ophthalmic management of mucopolysaccharidosis patients.

Eye Diseases↗