RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury

IntroductionGlaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand Aß, have been shown to mediate neuronal loss via internalizing Aß within the neurons. In this study, we investigated whether the RAGE–Aß axis plays a role in RGC loss in experimental glaucoma.MethodsRetinal ischemia was induced by an acute elevation of intraocular pressure in RAGE–/– and wild-type (WT) control mice. In a subset of animals, oligomeric Aß was injected directly into the vitreous of both strains. RGC loss was assessed using histology and biochemical assays. Baseline and terminal positive scotopic threshold (pSTR) were also recorded.ResultsRetinal ischemia resulted in 1.9-fold higher RGC loss in WT mice compared to RAGE–/– mice (36 ± 3% p < 0.0001 vs. 19 ± 2%, p = 0.004). Intravitreal injection of oligomeric Aß resulted in 2.3-fold greater RGC loss in WT mice compared to RAGE–/– mice, 7-days post-injection (55 ± 4% p = 0.008 vs. 24 ± 2%, p = 0.02). We also found a significant decline in the positive scotopic threshold response (pSTR) amplitude of WT mice compared to RAGE–/– (36 ± 3% vs. 16 ± 6%).DiscussionRAGE–/– mice are protected against RGC loss following retinal ischemia. Intravitreal injection of oligomeric Aß accelerated RGC loss in WT mice but not RAGE–/–. A co-localization of RAGE and Aß, suggests that RAGE–Aß binding may contribute to RGC loss

RVD: A Handheld Device-Based Fundus Video Dataset for Retinal Vessel Segmentation

Retinal vessel segmentation is generally grounded in image-based datasets collected with bench-top devices. The static images naturally lose the dynamic characteristics of retina fluctuation, resulting in diminished dataset richness, and the usage of bench-top devices further restricts dataset scalability due to its limited accessibility. Considering these limitations, we introduce the first video-based retinal dataset by employing handheld devices for data acquisition. The dataset comprises 635 smartphone-based fundus videos collected from four different clinics, involving 415 patients from 50 to 75 years old. It delivers comprehensive and precise annotations of retinal structures in both spatial and temporal dimensions, aiming to advance the landscape of vasculature segmentation. Specifically, the dataset provides three levels of spatial annotations: binary vessel masks for overall retinal structure delineation, general vein-artery masks for distinguishing the vein and artery, and fine-grained vein-artery masks for further characterizing the granularities of each artery and vein. In addition, the dataset offers temporal annotations that capture the vessel pulsation characteristics, assisting in detecting ocular diseases that require fine-grained recognition of hemodynamic fluctuation. In application, our dataset exhibits a significant domain shift with respect to data captured by bench-top devices, thus posing great challenges to existing methods. In the experiments, we provide evaluation metrics and benchmark results on our dataset, reflecting both the potential and challenges it offers for vessel segmentation tasks. We hope this challenging dataset would significantly contribute to the development of eye disease diagnosis and early prevention

Amplitude of retinal venous pulsations are associated with retinal nerve fibre layer thickness in glaucoma

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Non-invasive estimation of intracranial pressure by means of retinal venous pulsatility

Current techniques used to measure intracranial pressure (ICP) are invasive and require surgical procedures in order to implant pressure catheters in brain ventricles. The amplitude of central retinal vein pulsations (RVPa) has been shown to be associated with the pressure gradient between intraocular pressure (IOP) and ICP. When IOP approaches ICP, the pressure gradient drops, leading to cessation of RVPa. In this study we aim to investigate this relationship and define a new method to estimate ICP non-invasively. 10 healthy subjects (mean age 35±10) with clear medical history were included in this study. Baseline IOP was measured (Goldman tonometers) and RVP recorded using Dynamic Vessel Analyser.IOP was decreased actively using 0.5% Iopidine and RVP recorded simultaneously every 15 minutes. Digital signal processing techniques were used to measure mean RVP peak-to-peak amplitude in each cardiac cycle at different IOP levels. Linear regression equations were used to extract a relation between IOP and RVPa and to estimate the pressure at which RVPa cease (i.e. RVPa=0). At this point ICP equals IOP. IOP and ICP pressure waveforms were simulated in order to estimate ICP continuously. Results show a linear relationship between RVPa and IOP such that RVP decreases with IOP reduction. Estimated ICP ranged between 2-13.7 mmHg, all falling in the normal physiological range (i.e. 0-15 mmHg). Analysis of retinal venous pulsation in accordance with IOP may introduce a novel approach for estimation of ICP non-invasively.4 page(s

Systematic and Bibliometric Analysis of Magnetite Nanoparticles and Their Applications in (Biomedical) Research

Abstract Recent reports show air pollutant magnetite nanoparticles (MNPs) in the brains of people with Alzheimer's disease (AD). Considering various field applications of MNPs because of developments in nanotechnology, the aim of this study is to identify major trends and data gaps in research on magnetite to allow for relevant environmental and health risk assessment. Herein, a bibliometric and systematic analysis of the published magnetite literature (n = 31 567) between 1990 to 2020 is completed. Following appraisal, publications (n = 244) are grouped into four time periods with the main research theme identified for each as 1990–1997 “oxides,” 1998–2005 “ferric oxide,” 2006–2013 “pathology,” and 2014–2020 “animal model.” Magnetite formation and catalytic activity dominate the first two time periods, with the last two focusing on the exploitation of nanoparticle engineering. Japan and China have the highest number of citations for articles published. Longitudinal analysis indicates that magnetite research for the past 30 years shifted from environmental and industrial applications, to biomedical and its potential toxic effects. Therefore, whilst this study presents the research profile of different countries, the development in research on MNPs, it also reveals that further studies on the effects of MNPs on human health is much needed

Non-invasive intracranial pressure measurement using transcranial doppler sonography and support vector machines

Current techniques used for intracranial pressure (ICP) measurement are invasive. All require a surgical procedure for placement of a pressure catheter in the central nervous system (CNS) and therefore are associated with risk and morbidity. In this study we propose a noninvasive method for ICP measurement based on signal processing techniques.. In this method a non-linear relationship is used to determine ICP based on two more accessible parameters, namely arterial blood pressure (ABP) and the blood velocity of the middle cerebral artery (MCA) measured using the transcranial doppler (TCD) device. The clinical investigation of the proposed method shows high similarity between the invasively recorded intracranial pressure (ICP) and the predicted ICP using our proposed method under intensive care unit (ICU) conditions. A correlation of r=0.976 was achieved between the predicted ICP and the invasively ICP measurements, which shows a highly sensitive procedure in noninvasive ICP measurement.4 page(s

Autonomous assessment of spontaneous retinal venous pulsations in fundus videos using a deep learning framework

Abstract The presence or absence of spontaneous retinal venous pulsations (SVP) provides clinically significant insight into the hemodynamic status of the optic nerve head. Reduced SVP amplitudes have been linked to increased intracranial pressure and glaucoma progression. Currently, monitoring for the presence or absence of SVPs is performed subjectively and is highly dependent on trained clinicians. In this study, we developed a novel end-to-end deep model, called U3D-Net, to objectively classify SVPs as present or absent based on retinal fundus videos. The U3D-Net architecture consists of two distinct modules: an optic disc localizer and a classifier. First, a fast attention recurrent residual U-Net model is applied as the optic disc localizer. Then, the localized optic discs are passed on to a deep convolutional network for SVP classification. We trained and tested various time-series classifiers including 3D Inception, 3D Dense-ResNet, 3D ResNet, Long-term Recurrent Convolutional Network, and ConvLSTM. The optic disc localizer achieved a dice score of 95% for locating the optic disc in 30 milliseconds. Amongst the different tested models, the 3D Inception model achieved an accuracy, sensitivity, and F1-Score of 84 ± 5%, 90 ± 8%, and 81 ± 6% respectively, outperforming the other tested models in classifying SVPs. To the best of our knowledge, this research is the first study that utilizes a deep neural network for an autonomous and objective classification of SVPs using retinal fundus videos

Spontaneous retinal venous pulsatility in patients with cyanotic congenital heart disease

Spontaneous retinal venous pulsations (SRVP) are assessed as a clinical marker for patients with ophthalmic or neurological disorders. The pulsations are influenced by intraocular pressure (IOP), cerebrospinal fluid pressure (CSFp), and retinal venous pressure (RVP). However, little is known about the effect of cyanosis with polycythemia, a common finding in adults with complex congenital heart disease (CHD), on SRVP. This study investigated 11 subjects with long-standing cyanosis secondary to CHD and 11 control subjects to determine if there were measurable differences in resting pulsatility for a given IOP level. Intraocular pressure was measured using Goldman tonometry, and dynamic SRVP was recorded noninvasively using a retinal vessel imaging system. Peak amplitude of SRVP at each cardiac cycle was measured and compared with IOP. Heart rate was also monitored during the tests. Results show that for a similar baseline IOP, SRVP amplitudes are significantly lower in cyanotic patients compared with normal subjects (P < 0.0001). This may be explained by an increased RVP or high CSFp in these patients. Mean venous diameter is also significantly higher in cyanotic patients (P < 0.01), but no significant relationship was found between SRVP or diameter with blood parameters. © 2011 Springer

Cognitive Performance on the Montreal Cognitive Assessment Test and Retinal Structural and Functional Measures in Glaucoma

Background: Glaucoma, the leading cause of irreversible blindness, is classified as a neurodegenerative disease, and its incidence increases with age. Pathophysiological changes, such as the deposition of amyloid-beta plaques in the retinal ganglion cell layer, as well as neuropsychological changes, including cognitive decline, have been reported in glaucoma. However, the association between cognitive ability and retinal functional and structural measures in glaucoma, particularly glaucoma subtypes, has not been studied. We studied the association between cognitive ability and the visual field reliability indices as well as the retinal ganglion cell (RGC) count estimates in a cohort of glaucoma patients. Methods: A total of 95 eyes from 61 glaucoma patients were included. From these, 20 were normal-tension glaucoma (NTG), 25 were primary open-angle glaucoma (POAG), and 16 were glaucoma suspects. All the participants had a computerised Humphrey visual field (HVF) assessment and optical coherence tomography (OCT) scan and were administered the written Montreal Cognitive Assessment (MoCA) test. RGC count estimates were derived based on established formulas using the HVF and OCT results. A MoCA cut-off score of 25 and less was designated as cognitive impairment. Student&rsquo;s t-test was used to assess differences between the groups. The Pearson correlation coefficient was used to assess the association between MoCA scores and retinal structural and functional measures. Results: Significant associations were found between MoCA scores and the false-negative and pattern standard deviation indices recorded on the HVF (r = &minus;0.19, r = &minus;0.22, p &lt; 0.05). The mean IOP was significantly lower in the cognitively impaired group (i.e., MOCA &le; 25) (13.7 &plusmn; 3.6 vs. 15.7 &plusmn; 4.5, p &lt; 0.05). No significant association was found between RGC count estimates and MoCA scores. Analysis of these parameters in individual glaucoma subtypes did not reveal any group-specific significant associations either