Combined use of parallel-plate compression and finite element modeling to analyze the mechanical properties of intact porcine lens

The objective of this study is to explore the feasibility of a compression test for measuring mechanical properties of intact eye lenses using novel parallel plate compression equipment to compare the accuracy of implementing a classical Hertzian model and a newly proposed adjusted Hertzian model to calculate Young’s modulus from compression test results using finite element (FE) analysis. Parallel-plate compression tests were performed on porcine lenses. An axisymmetric FE model was developed to simulate the experimental process to evaluate the accuracy of using the classical Hertzian theory of contact mechanics as well as a newly proposed adjusted Hertzian theory model for calculating the equivalent Young’s modulus. By fitting the force-displacement relation obtained from FE simulations to both the classical and adjusted Hertzian theory model and comparing the calculated modulus to the input modulus of the FE model, the results demonstrated that the classical Hertzian theory model overestimated the Young’s modulus with a proportional error of over 10%. The adjusted Hertzian theory model produced results that are closer to original input values with error ratios all lower than 1.29%. Measurements of three porcine lenses from the parallel plate compression experiments were analyzed with resulting values of Young’s modulus of between 3.2kPa and 4.3kPa calculated. This study demonstrates that the adjusted Hertzian theory of contact mechanics can be applied in conjunction with the parallel-plate compression system to investigate the overall mechanical behavior of intact lenses

Community-based family and carer-support programmes for children with disabilities

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordChildren and young people (CYP) with disabilities face multiple challenges and unmet health needs. There is considerable variability in quality of health services across the UK for these children. Families report that they experience lack of information or misinformation about health, social care and education of their child. They also highlight a desire to engage with other families of CYP with disabilities. There is growing evidence that community-based group interventions in under-resourced settings are effective at improving quality of life for both CYP with disabilities and caregivers. Few similar interventions or evidence exists in the UK. This article provides an overview of relevant evidence and, using cerebral palsy as an exemplar, discusses the potential for group-based programmes for parent carers in the UK. Groups would aim to address information needs, support providers to deliver evidence-based care, and thereby improve the health and wellbeing of CYP with disabilities

The importance of parameter choice in modelling dynamics of the eye lens

The lens provides refractive power to the eye and is capable of altering ocular focus in response to visual demand. This capacity diminishes with age. Current biomedical technologies, which seek to design an implant lens capable of replicating the function of the biological lens, are unable as yet to provide such an implant with the requisite optical quality or ability to change the focussing power of the eye. This is because the mechanism of altering focus, termed accommodation, is not fully understood and seemingly conflicting theories require experimental support which is difficult to obtain from the living eye. This investigation presents finite element models of the eye lens based on data from human lenses aged 16 and 35 years that consider the influence of various modelling parameters, including material properties, a wide range of angles of force application and capsular thickness. Results from axisymmetric models show that the anterior and posterior zonules may have a greater impact on shape change than the equatorial zonule and that choice of capsular thickness values can influence the results from modelled simulations

Cataract-Causing Defect of a Mutant γ-Crystallin Proceeds through an Aggregation Pathway Which Bypasses Recognition by the α-Crystallin Chaperone

Background: The transparency of the eye lens depends upon maintenance of the native state of the γ- and β-crystallins, which is aided by the abundant chaperones αA- and αB-crystallin. Mature onset cataract, the leading cause of blindness worldwide, involves the polymerization of covalently damaged or partially unfolded crystallins into light-scattering aggregates. A number of single amino acid substitutions and truncations of γ-crystallins result in congenital cataract in both humans and mice, though in many cases the coupling between the protein alterations and the accumulation of aggregates is poorly defined. Methodology/Principal Findings: We have studied the aggregation properties and chaperone interactions of human γD-crystallin carrying substitutions of two buried core mutants, I90F and V75D, which cause congenital cataract in mice. The in vitro aggregation pathway competing with productive refolding was not altered by either substitution. Furthermore, this aggregation pathway for both mutant proteins–originating from a partially folded intermediate–was efficiently suppressed by αB-crystallin. Thus the cataract pathology was unlikely to be associated with a direct folding defect. The native state of wild-type human γD-crystallin exhibited no tendency to aggregate under physiological conditions. However both I90F and V75D native-like proteins exhibited slow (days) aggregation to high molecular weight aggregates under physiological conditions. The perturbed conformation of I90F was recognized and bound by both αA and αB chaperones. In contrast, the aggregation derived from the perturbed state of V75D was not suppressed by either chaperone, and the aggregating species were not bound by the chaperone. Conclusions/Significance: The cataract phenotype of I90F in mice may be due to premature saturation of the finite α- crystallin pool. The V75D aggregation pathway and its escape from chaperone surveillance and aggregation suppression can account for the congenital cataract pathology of this mutant. Failure of chaperone recognition may be an important source of pathology for many other protein folding defects.National Eye Institute (Grant no. EY015834 )National Institutes of Health (U.S.) (Grant no. GM17980

Age-related development of a refractive index plateau in the human lens: evidence for a distinct nucleus

The human lens comprises two distinct regions in which the refractive index changes at different rates. The periphery contains a rapidly increasing refractive index gradient, which becomes steeper with age. The inner region contains a shallow gradient, which flattens with age, due to formation of a central plateau, of RI = 1.418, which reaches a maximum size of 7.0 × 3.05 mm around age 60 years. Formation of the plateau can be attributed to compression of fibre cells generated in prenatal life. Present in prenatal but not in postnatal fibre cells, γ-crystallin may play a role in limiting nuclear cell compression

Are Ancient Proteins Responsible for the Age-Related Decline in Health and Fitness?

There are a number of sites in the body where proteins are present for decades and sometimes for all of our lives. Over a period of many years, such proteins are subject to two types of modifications. The first results from the intrinsic instability of certain amino acid residues and leads to deamidation, racemization, and truncation. The second type can be traced to relentless covalent modification of such ancient proteins by reactive biochemicals produced during cellular metabolism.The accumulation of both types of posttranslational modifications over time may have important consequences for the properties of tissues that contain such proteins. It is proposed that the age-related decline in function of organs such as the eye, heart, brain, and lung, as well as skeletal components, comes about, in part, from the posttranslational modification of these long-lived proteins. Examples are provided in which this may be an important factor in the etiology of age-related conditions. As the properties of these proteins alter inexorably over time, the molecular changes contribute to a gradual decline in the function of individual organs and also tissues such as joints. This cumulative degeneration of old proteins at multiple sites in the body may also constrain the ultimate life span of the individual. The human lens may be particularly useful for discovering which reactive metabolites in the body are of most importance for posttranslational modification of long-lived proteins