Microglia: Key Players in Retinal Ageing and Neurodegeneration

Microglia are the resident immune cells of the central nervous system (CNS) and play a key role in maintaining the normal function of the retina and brain. During early development, microglia migrate into the retina, transform into a highly ramified phenotype, and scan their environment constantly. Microglia can be activated by any homeostatic disturbance that may endanger neurons and threaten tissue integrity. Once activated, the young microglia exhibit a high diversity in their phenotypes as well as their functions, which relate to either beneficial or harmful consequences. Microglial activation is associated with the release of cytokines, chemokines, and growth factors that can determine pathological outcomes. As the professional phagocytes in the retina, microglia are responsible for the clearance of pathogens, dead cells, and protein aggregates. However, their phenotypic diversity and phagocytic capacity is compromised with ageing. This may result in the accumulation of protein aggregates and myelin debris leading to retinal neuroinflammation and neurodegeneration. In this review, we describe microglial phenotypes and functions in the context of the young and ageing retina, and the mechanisms underlying changes in ageing. Additionally, we review microglia-mediated retinal neuroinflammation and discuss the mechanisms of microglial involvement in retinal neurodegenerative diseases

Ocular Manifestations of Alzheimer's Disease in Animal Models

Alzheimer's disease (AD) is the most common form of dementia, and the pathological changes of senile plaques (SPs) and neurofibrillary tangles (NFTs) in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an extension of the brain; the retina. Due to the optically transparent nature of the eye, it is possible to image the retina at a cellular level noninvasively and thus potentially allow an earlier diagnosis as well as a way of monitoring progression and treatment effects. Transgenic animal models expressing amyloid precursor protein (APP) presenilin (PS) and tau mutations have been used successfully to recapitulate the pathological findings of AD in the brain. This paper will cover the ocular abnormalities that have been detected in these transgenic AD animal models

Deep learning to detect macular atrophy in wet age-related macular degeneration using optical coherence tomography

Here, we have developed a deep learning method to fully automatically detect and quantify six main clinically relevant atrophic features associated with macular atrophy (MA) using optical coherence tomography (OCT) analysis of patients with wet age-related macular degeneration (AMD). The development of MA in patients with AMD results in irreversible blindness, and there is currently no effective method of early diagnosis of this condition, despite the recent development of unique treatments. Using OCT dataset of a total of 2211 B-scans from 45 volumetric scans of 8 patients, a convolutional neural network using one-against-all strategy was trained to present all six atrophic features followed by a validation to evaluate the performance of the models. The model predictive performance has achieved a mean dice similarity coefficient score of 0.706 ± 0.039, a mean Precision score of 0.834 ± 0.048, and a mean Sensitivity score of 0.615 ± 0.051. These results show the unique potential of using artificially intelligence-aided methods for early detection and identification of the progression of MA in wet AMD, which can further support and assist clinical decisions

Recod @ Mediaeval 2014: Diverse Social Images Retrieval

This paper presents the results of the rst participation of our multi-institutional team in the Retrieving Diverse Social Images Task at MediaEval 2014. In this task we were required to develop a summarization and diversi cation approach for social photo retrieval. Our approach is based on irrelevant image ltering, image re-ranking, and diversity promotion by clustering. We have used visual and textual features, including image metadata and user credibility information.1263Carbonell, J., Goldstein, J., The use of mmr, diversity-based reranking for reordering documents and producing summaries (1998) SIGIR, pp. 335-336Ionescu, B., Popescu, A., Lupu, M., Gînscâ, A.L., MüLler, H., Retrieving diverse social images at mediaeval 2014: Challenge, dataset and evaluation (2014) MediaEval 2014 Workshop, , BarcelonaPenatti, O.A.B., Valle, E., Da Torres, R.S., Comparative study of global color and texture descriptors for web image retrieval (2012) J. Vis. Commun. Image Repr., 23 (2), pp. 359-38

Hemiselmis andersenii and Chlorella stigmatophora as new sources of high‐value compounds: a lipidomic approach

To unlock the potential of Chlorella stigmatophora (Trebouxiophyceae, Chlorophyta) and Hemiselmis andersenii (Cryptophyceae, Cryptophyta) as natural reactors for biotechnological exploitation, their lipophilic extracts were characterized using Fourier Transform Infrared spectroscopy with Attenuated Total Reflectance (FTIR-ATR) and Gas Chromatography-Mass Spectrometry (GC-MS) before and after alkaline hydrolysis. The GC-MS analysis enabled the identification of 62 metabolites-namely fatty acids (27), aliphatic alcohols (17), monoglycerides (7), sterols (4), and other compounds (7). After alkaline hydrolysis, monounsaturated fatty acids increased by as much as 87%, suggesting that the esterified compounds were mainly neutral lipids. Hemiselmis andersenii yielded the highest Σω3/Σω6 ratio (7.26), indicating that it is a good source of ω3 fatty acids, in comparison to C. stigmatophora (Σω3/Σω6 = 1.24). Both microalgae presented significant amounts of aliphatic alcohols (6.81-10.95 mg · g dw-1 ), which are recognized by their cholesterol-lowering properties. The multivariate analysis allowed visualization of the chemical divergence among H. andersenii lipophilic extracts before and after alkaline hydrolysis, as well as species-specific differences. Chlorella stigmatophora showed to be a valuable source of essential fatty acids for nutraceuticals, whereas H. andersenii, due to its high chemical diversity, seems to be suitable for different fields of application.info:eu-repo/semantics/publishedVersio

Fiber association and network formation in PLA/lignocellulosic fiber composites.

PLA composites were prepared in an internal mixer with a lignocellulosic fiber having relatively large aspect ratio. Fiber content changed between 0 and 60 vol% and the homogenized material was compression molded to 1 mm thick plates. The composites showed anomalous behavior above certain fiber content. Their modulus and especially their strength decreased drastically and modeling also proved the loss of reinforcement at large fiber contents. Micromechanical testing showed that the mechanism of deformation and failure changes at a critical fiber content. Microscopic analysis indi-cated the formation of a network purely from geometrical reasons. The inherent strength of the network is very small because of the weak forces acting among the fibers. This weak inherent strength makes the structure of the composites very sensitive to pro-cessing conditions, and decreases strength, reproducibility as well as reliability

Topology Control in Cooperative Ad Hoc Wireless Networks

AbstractCooperative communication (CC) is a technique that exploits spatial diversity allowing multiple nodes to cooperatively relay signals to the receiver so that it can combine the received signals to obtain the original message. CC can be combined with topology control to increase connectivity at the cost of a small increase in energy consumption. This work focuses on exploring CC to improve the connectivity with a sink node in ad hoc wireless networks. More precisely, this work proposes a new technique, named CoopSink, that combines CC and topology control techniques to increase connectivity to a sink node while ensuring energy-efficient routes. Simulation results show that connectivity and routing to the sink cost can be improved up to 6.8 and 2.3 times, respectively, when compared with other similar strategies

Simultaneous co-delivery of neuroprotective drugs from multiloaded PLGA microspheres for the treatment of glaucoma

Glaucoma is a multifactorial neurodegenerative disorder and one of the leading causes of irreversible blindness globally and for which intraocular pressure is the only modifiable risk factor. Although neuroprotective therapies have been suggested to have therapeutic potential, drug delivery for the treatment of ocular disorders such as glaucoma remains an unmet clinical need, further complicated by poor patient compliance with topically applied treatments. In the present study we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating three recognised neuroprotective agents (dexamethasone (DX), melatonin (MEL) and coenzyme Q10 (CoQ10)) in a single formulation (DMQ-MSs) to create a novel sustained-release intraocular drug delivery system (IODDS) for the treatment of glaucoma. MSs were spherical, with a mean particle size of 29.04 ± 1.89 μm rendering them suitable for intravitreal injection using conventional 25G-32G needles. Greater than 62% incorporation efficiency was achieved for the three drug cargo and MSs were able to co-deliver the encapsulated active compounds in a sustained manner over 30-days with low burst release. In vitro studies showed DMQ-MSs to be neuroprotective in a glutamate-induced cytotoxicity model (IC50 10.00±0.94 mM versus 6.89±0.82 mM in absence of DMQ-MSs) in R28 cell line. In vivo efficacy studies were performed using a well-established rodent model of chronic ocular hypertension (OHT), comparing single intravitreal injections of microspheres of DMQ-MSs to their equivalent individual single drug loaded MSs mixture (MSsmix), empty MSs, no-treatment OHT only and naïve groups. Twenty one days after OHT induction, DMQ-MSs showed a significantly neuroprotective effect on RGCs compared to OHT only controls. No such protective effect was observed in empty MSs and single-drug MSs treated groups. This work suggests that multi-loaded PLGA MSs present a novel therapeutic approach in the management of retinal neurodegeneration conditions such as glaucoma

Integration of bow-tie plasmonic nano-antennas on tapered fibers

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPIn this article, a new and flexible approach to control the electric field enhancement of bow-tie nano-antennas by integrating them on the lateral of a tapered optical fiber is proposed. The device is driven by a Q-switched laser and the performance of a fabricated nano-antenna in a quartz slide is tested by a Surface Enhanced Raman Scattering (SERS) experiment. A refractive index sensing experiment is also performed and a sensitivity of (240 +/- 30) nm/RIU is found in the 1.33-1.35 index range.25889868996FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2014/50632-6The Asian Office of Aerospace Research and Development (AOARD US Air Force FA2386-15-1-4084); Australian Research Council (ARC LP160100253); and Sao Paulo Research Foundation (FAPESP) (#2014/50632-6)

Treatment of Advanced Glaucoma Study:a multicentre randomised controlled trial comparing primary medical treatment with primary trabeculectomy for people with newly diagnosed advanced glaucoma-study protocol

Funding Nottingham University Hospitals NHS Trust sponsors the trial and provides the necessary trial insurance. The trial is funded by a grant awarded by the Health Technology Assessment (NIHR HTA) programme (project number 12/35/38).Peer reviewedPublisher PD