Contribution of genetic and environmental effects on lens thickness: the Guangzhou Twin Eye study.

PURPOSE:

This study investigated the heritability of lens thickness (LT) and relative lens thickness (LT/axial length, rLT) measured by Lenstar among Chinese children and adolescents in the Guangzhou Twin Eye study.

METHODS:

Twins aged 8 to 22 years were enrolled from the Guangzhou Twin Registry. A series of LT and axial length (AL) measurements using the Lenstar were taken for each twin. Zygosity was confirmed by genotyping in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling, after adjustment for age and sex with the Mx program.

RESULTS:

Seven hundred sixty-eight twin pairs (482 monozygotic [MZ] and 286 dizygotic [DZ] twins) were available for data analysis. The mean (standard deviation) LT and rLT were 3.45 (0.18) mm and 0.142 (0.01), respectively. The intraclass correlation coefficients (ICCs) for LT were 0.90 for the MZ and 0.39 for the DZ twins; and those for rLT were 0.90 for the MZ and 0.40 for the DZ twins, respectively. The best-fitting model yielded 89.5% (95% CI: 87.8%-91.0%) of additive genetic effects and 10.5% (95% CI: 9.0%-12.2%) of unique environmental effects for LT, and 89.3% (95% CI: 89.2%-89.3%) of additive genetic effects and 10.7% (95% CI: 10.7%-11.4%) of unique environmental effects for rLT.

CONCLUSIONS:

This study confirms that the LT in young healthy subjects may be mainly affected by additive genetic factors. High heritability remains even when the data are corrected for the influence of AL with the use of rLT.

Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis

Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells.

The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease

Introduction
Standard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.

Methods
The Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.

Discussion
This trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.

The Negligent Eye

An exhibition which explores artists use of scanners and the implications of this form of mediation. the exhibition aims to explore the social philosophical and aesthetic implications of scanning both as a technology and a form of attention due to the ever increasing speed of image circulation and production.This builds on former research such as Print in 3D at the V&A in 2009.

Feasibility of Undertaking Off-Site Infant Eye-Tracking Assessments of Neuro-Cognitive Functioning in Early-Intervention Centres

Recent work suggests that differences in functional brain development are already identifiable in 6- to 9-month-old infants from low socio-economic status (SES) backgrounds. Investigation of early SES-related differences in neuro-cognitive functioning requires the recruitment of large and diverse samples of infants, yet it is often difficult to persuade low-SES parents to come to a university setting. One solution is to recruit infants through early intervention children’s centres (CCs). These are often located in areas of high relative deprivation to support young children. Given the increasing portability of eye-tracking equipment, assessment of large clusters of infants could be undertaken in centres by suitably trained early intervention staff. Here, we report on a study involving 174 infants and their parents, carried out in partnership with CCs, exploring the feasibility of this approach. We report the processes of setting up the project and participant recruitment. We report the diversity of sample obtained on the engagement of CC staff in training and the process of assessment itself.We report the quality of the data obtained, and the levels of engagement of parents and infants. We conclude that this approach has great potential for recruiting large and diverse samples worldwide, provides sufficiently reliable data and is engaging to staff, parents and infants.

A study on dynamic state information (DSI) around users for safe urban life

To select each node by devices and by contexts in urban computing, users have to put their plan information and their requests into a computing environment (ex. PDA, Smart Devices, Laptops, etc.) in advance and they will try to keep the optimized states between users and the computing environment. However, because of bad contexts, users may get the wrong decision, so, one of the users’ demands may be requesting the good server which has higher security. To take this issue, we define the structure of Dynamic State Information (DSI) which takes a process about security including the relevant factors in sending/receiving contexts, which select the best during user movement with server quality and security states from DSI. Finally, whenever some information changes, users and devices get the notices including security factors, then an automatic reaction can be possible; therefore all users can safely use all devices in urban computing.

Analysis of polycyclic aromatic hydrocarbons in fish: evaluation of a quick, easy, cheap, effective, rugged, and safe extraction method

QuEChERS method was evaluated for extraction of 16 PAHs from fish samples. For a selective measurement of the compounds, extracts were analysed by LC with fluorescence detection. The overall analytical procedure was validated by systematic recovery experiments at three levels and by using the standard reference material SRM 2977 (mussel tissue). The targeted contaminants, except naphthalene and acenaphthene, were successfully extracted from SRM 2977 with recoveries ranging from 63.5–110.0% with variation coefficients not exceeding 8%. The optimum QuEChERS conditions were the following: 5 g of homogenised fish sample, 10 mL of ACN, agitation performed by vortex during 3 min. Quantification limits ranging from 0.12– 1.90 ng/g wet weight (0.30–4.70 µg/L) were obtained. The optimized methodology was applied to assess the safety concerning PAHs contents of horse mackerel (Trachurus trachurus), chub mackerel (Scomber japonicus), sardine (Sardina pilchardus) and farmed seabass (Dicentrarchus labrax). Although benzo(a)pyrene, the marker used for evaluating the carcinogenic risk of PAHs in food, was not detected in the analysed samples (89 individuals corresponding to 27 homogenized samples), the overall mean concentration ranged from 2.52 l 1.20 ng/g in horse mackerel to 14.6 ± 2.8 ng/ g in farmed seabass. Significant differences were found between the mean PAHs concentrations of the four groups.

Diane Arbus: the wonderful wizard of odds or the poetics of the i (eye)

Diane Arbus‘ photographs are mainly about difference. Most of the time she is trying ‗[…] to suppress, or at least reduce, moral and sensory queasiness‘ (Sontag 1977: 40) in order to represent a world where the subject of the photograph is not merely the ‗other‘ but also the I. Her technique does not coax her subjects into natural poses. Instead she encourages them to be strange and awkward. By posing for her, the revelation of the self is identified with what is odd. This paper aims at understanding the geography of difference that, at the same time, is also of resistance, since Diane Arbus reveals what was forcefully hidden by bringing it into light in such a way that it is impossible to ignore. Her photographs display a poetic beauty that is not only of the ‗I‘ but also of the ‗eye‘. The world that is depicted is one in which we are all the same. She ―atomizes‖ reality by separating each element and ‗Instead of showing identity between things which are different […] everybody is shown to look the same.‘ (Sontag 1977: 47). Furthermore, this paper analyses some of Arbus‘ photographs so as to explain this point of view, by trying to argue that between rejecting and reacting against what is standardized she does not forget the geography of the body which is also a geography of the self. While creating a new imagetic topos, where what is trivial becomes divine, she also presents the frailty of others as our own.

Are coffee silverskin extracts safe for topical use? An in vitro and in vivo approach

Recent changes in regulatory requirements and social views on animal testing have incremented the development of reliable alternative tests for predicting skin and ocular irritation potential of products based on new raw materials. In this regard, botanical ingredients used in cosmetic products are among those materials, and should be carefully reviewed concerning the potential presence of irritant constituents. In particular, cosmetic products used on the face, in vicinity of the eyes or that may come in contact with mucous membranes, should avoid botanical ingredients that contain, or are suspected to contain, such ingredients. In this study, we aimed to evaluate the effect of a new cosmetic ingredient, namely, coffee silverskin (CS), with an in vitro skin and ocular irritation assay using reconstructed human epidermis, EpiSkin™, and human corneal epithelial model, SkinEthics™ HCE, and an in vivo assay. Three different extracts of CS were evaluated. The histology of the models after extracts applications was analysed. The in vitro results demonstrated that extracts were not classified as irritant and the histological analyses proved that extracts did not affect both models structure. The content of caffeine, 5-hydroxymethyl furfural and chlorogenic acid was quantified after the epidermal assay. The in vivo test carried out with the most promising extract (hydroalcoholic) showed that, with respect to irritant effects, these extracts can be regarded as safe for topical application.

New roles of Rab GTPases on eye diseases: targeting VEGF secretion

RESUMO: A retina é composta, entre outras estruturas, pelo epitélio pigmentar da retina (EPR)e pela coróide. A região central da retina denomina-se mácula, e é a zona mais afetada na degenerescência macular relacionada com a idade, a forma mais comum de degenerescência da retina. Nesta doença, a secreção de fatores de crescimento pelo EPR é afetada, nomeadamente a do fator de crescimento vascular endotelial (VEGF), e pouco se sabe ainda sobre os mecanismos moleculares conducentes a esta condição. A família de proteínas Rab GTPases está envolvida nas vias intracelulares de sinalização e tráfego membranares, essenciais na transdução de sinais extracelulares em respostas biológicas. A sua crucial importância nestes mecanismos levou-nos a considerar o seu potencial envolvimento nas vias de secreção do VEGF, e a questionar-nos se teriam algum papel regulador sobre as mesmas. O principal objetivo deste trabalho é identificar Rab GTPases importantes para as vias de secreção e endocitose do VEGF no EPR. Essa identificação ajudará a esclarecer a patogénese da degenerescência macular da retina, e poderá servir para uma procura mais direcionada de novos agentes terapêuticos. A caracterização de dois modelos in vitro do EPR, células primárias isoladas de murganho e a linha celular B6-RPE07,levou-nos a concluir que são ambos semelhantes. Contudo, a linha celular foi escolhida como protótipo do EPR por permitir o acesso a um número ilimitado de células. No decurso deste trabalho, desenvolvemos e caracterizámos uma biblioteca de ferramentas moleculares que nos permitiram reduzir os níveis proteicos das proteínas Rab GTPases, com base na tecnologia de ácido ribonucleico (ARN) de interferência. O papel das proteínas Rab GTPases na secreção do VEGF no EPR foi estudado com base no silenciamento de apenas uma proteína, ou combinando várias, segundo a sua localização e funções intracelulares descritas. Este trabalho permitiu-nos concluir que as proteínas Rab GTPases são importantes intervenientes no processo de secreção de VEGF pelo EPR, e confirmar dados anteriores que relatam o envolvimento de algumas Rab GTPases endocíticas no processo. Propomos ainda um novo modelo para a interação destas proteínas no EPR, e sugerimos que a Rab10 e a Rab14 atuam negativamente sobre a Rab8, controlando o seu funcionamento. Os nossos resultados evidenciam a importância das proteínas Rab GTPases na secreção do VEGF pelas células do EPR, e servem de base a futuros estudos que melhor procurem compreender este mecanismo e de que modo a sua alteração se relaciona com a degenerescência da retina.--------ABSTRACT: Retinal pigment epithelium (RPE) and choroid are components of the mammalian retina, of which the central region is called macula. The most common form of retinaldegeneration, age-related macular degeneration (AMD), involves primarily deregulation of growth factors secretion by the RPE. Very little is known about the molecular mechanisms that lead to impairment of RPE’s homeostatic intracellular processes, namely the secretion of vascular endothelial growth factor (VEGF). Rab GTPases’ family regulates membrane targeting and traffic, being essential in the transduction of signal pathways. Given Rab proteins’ role in intracellular trafficking, we propose to identify key regulatory Rab proteins involved in either the secretory or the recycling pathways of VEGF in RPE. Understanding how Rab proteins’ function disruption could lead to retinal and choroidal pathology would ultimately contribute to find new therapeutic agents. Here, we characterized two mouse RPE in vitro cell models, primary cells and B6-RPE07 cell line, and concluded that both display important epithelial features as the RPE presents in vivo. Considering unlimited cell number and results reproducibility, we chose B6-RPE07 cells to further study Rab proteins’ function. To scrutinize the consequences of Rab proteins’ absence or diminished levels, we have developed novel molecular tools to achieve silencing of these key proteins using miRNA technology. We further addressed the effect of Rab proteins’ absence on VEGF secretion by performing an extensive screening where different Rab proteins were silenced, both individually and in multiple combinations considering their cellular/ compartment location. We conclude that Rab GTPases are important intervenients in VEGF secretion by RPE cells, confirming endocytic Rab proteins’ role in regulation of VEGF biology. We also propose a novel model for Rab proteins’ interaction in RPE. Our results suggest that Rab10 and Rab14 might influence Rab8 in a negative feedback mechanism, important for controlling VEGF secretion. Our achievements’ unravel Rab proteins’ role in VEGF secretion by RPE cells and are the basis for future studies to better understand RPE molecular secretory machinery.

Safe dissection of the distally based anterolateral thigh flap.

Background The distally based anterolateral thigh (ALT) flap is an interesting reconstructive solution for complex soft tissue defects of the knee. In spite of a low donor site morbidity and wide covering surface as well as arch of rotation, it has never gained popularity among reconstructive surgeons. Venous congestion and difficult flap dissection in the presence of a variable anatomy of the vascular pedicle are the possible reasons.Methods An anatomical study of 15 cadaver legs was performed to further clarify the blood supply of the distally based ALT. Our early experience with the use of preoperative angiography and a safe flap design modification that avoids distal intramuscular skeletonization of the vascular pedicle and includes a subcutaneous strip ranging from the distal end of the flap to the pivot point is presented.Results The distally based ALT presents a constant and reliable retrograde vascular contribution from the superior genicular artery. Preoperative angiography reliably identified and avoided critical Shieh Type II pedicled flaps. The preservation of a subcutaneous strip ranging from the distal flap end to the upper knee was associated with the absence of venous congestion in a short case series.Conclusions Preoperative angiography and a flap design modification are proposed to allow the safe transfer of the distally based ALT to reconstruct soft tissue defects of the knee.