Retinal ganglion cell responses to lesion and their prevention

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Inmunología, Oftalmología y Otorrinolaringología, leída el 20-12-2021Las células ganglionares de la retina (CGR) son las únicas células de la retina que envían la información de la retina al cerebro y por ello son indispensables para la visión. Se trata de una población heterogénea ya que se ha documentado que comprende hasta 46 tipos celulares diferentes en el ratón. Los diferentes tipos de CGR codifican un aspecto particular de la información visual y la transmiten al cerebro para realizar funciones formadoras de imagen (FI) o no formadoras de imagen (NFI). Un tipo de CGR contiene el pigmento visual melanopsina, lo que le permite realizar fototransducción y por ello se denomina CGR intrínsecamente fotosensible (CGRif).Se han descrito hasta 6 tipos de CGRif en el ratón que realizan las funciones NFI de nuestro sistema visual. Los diferentes tipos de CGR responden de un modo diferente a diferentes tipos de lesión y también a la neuroprotección...The Retinal Ganglion Cells (RGCs) are the only retinal cells that send information to the brain and thus are essential for vision. It is a heterogeneous population since up to 46 different RGC types have been documented in mice. The different RGC types encode a particular aspect of visual information and send it to the brain, where theycontribute to image forming (IF) and non-image forming (NIF) visual functions. A type of RGC contains the visual pigment melanopsin and performs phototransductionand thus has been named intrinsically photosensitive RGC (ipRGC). Six types of ipRGCs have been described in mice that perform the NIF functions of the visual system. Recent studies have documented that the different RGC types respond differently to different types of injury and to neuroprotection...Fac. de MedicinaTRUEunpu

Impact of anthropogenic activities on an urban river through a comprehensive analysis of water and sediments

In this study, the aim of this study was to assess the impact of urban and industrial areas on an urban river through a comprehensive analysis of water and sediments.Six different sites along San Luis river, Argentina, were characterized by measuring 12 physical-chemical parameters and nine heavy metals according to standard protocols. Metal pollution in sediment samples was evaluated with several indices. Cluster analysis was applied to standardized experimental data in order to study spatial variability. As, Cu, Cr, Mn, Pb and Zn were the main contributors to sediment pollution, and the industrial zone studied showed moderate enrichment of Co, Cu and Zn, probably due to anthropogenic activities. Cluster analysis allowed the grouping of the sites: sediment samples were classified into two clusters according to the metal content; water samples were arranged into three groups according to organic matter content. The results were compared with sediment and water quality guidelines. They indicated progressive deterioration of water and sediment quality compared with the background area, mainly in the sites following the industrial park and domestic discharge areas. Moreover, the results showed that the analysis of both water and sediment should be considered to achieve a watershed contamination profile.Fil: Castro, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Almeida, César Américo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Bazán, Cristian Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Vidal, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Delfini, Claudio Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Villegas, Liliana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentin

Multimodal Imaging, OCT en Face, and OCT Angiography of an Anomalous Retinal Artery: Case Report and Review of the Literature

The purpose is to study for the first time the vascular plexuses and the retinal nerve fiber layer and raphe of a patient with a very uncommon anatomical variation: an anomalous retinal artery supplying the whole macula. We used multimodal imaging, en face spectral-domain optic coherence tomography, and spectral-domain optic coherence tomography angiography. One patient presented in his left eye a very unusual anatomical variation of macular vascularization. A retinal artery deriving from the inferior temporal retinal artery irrigated the whole macula. The formation of the papillomacular bundle and the temporal raphe nerve fiber layer has been attributed to the earlier development of the central retina and to the existence of 2 distinct watershed zones. However, there are very uncommon anatomical variations of the retinal vasculature in which large retinal vessels cross the raphe and could influence the morphology and structure of the nerve fiber layer of the posterior pole. We review the literature on the subject and document for the first time an anomalous artery that irrigates the whole macula, normal thickness and morphology of the nerve fiber layer, and the temporal raphe

Novel Insights into the Transmission of SARS-CoV-2 Through the Ocular Surface and its Detection in Tears and Conjunctival Secretions: A Review

SARS-CoV-2 is a highly transmissible virus that spreads mainly via person-to-person contact through respiratory droplets, or through contact with contaminated objects or surfaces from an infected person. At present we are passing through a phase of slow and painful understanding of the origin, epidemiological profile, clinical spectrum, and risk profile of the virus. To the best of our knowledge there is only limited and contradictory evidence concerning SARS-CoV-2 transmission through other routes. Importantly, the eye may constitute not only a potential site of virus replication but also an alternative transmission route of the virus from the ocular surface to the respiratory and gastrointestinal tract. It is therefore imperative to gain a better insight into the potential ophthalmological transmission route of the virus and establish directions on best practice and future models of care for ophthalmological patients. This review article critically evaluates available evidence on the ophthalmological mode of viral transmission and the value of earlier identification of the virus on the eye. More evidence is urgently needed to better evaluate the need for protective measures and reliable ocular diagnostic tests to diminish further pandemic spread

Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity

We studied short- and long-term effects of intravitreal injection of N-methyl-d-aspartate (NMDA) on melanopsin-containing (m+) and non-melanopsin-containing (Brn3a+) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using Spectral Domain-Optical Coherence Tomography (SD-OCT). Ex vivo analyses were done at 3, 7, or 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for brain-specific homeobox/POU domain protein 3A (Brn3a) and melanopsin (m), the total number of Brn3a+RGCs and m+RGCs were quantified, and their topography represented. In control retinas, the mean total numbers of Brn3a+RGCs and m+RGCs were 78,903 ± 3572 and 2358 ± 144 (mean ± SD; n = 10), respectively. In the NMDA injected retinas, Brn3a+RGCs numbers diminished to 49%, 28%, 24%, and 19%, at 3, 7, 14 days, and 15 months, respectively. There was no further loss between 7 days and 15 months. The number of immunoidentified m+RGCs decreased significantly at 3 days, recovered between 3 and 7 days, and were back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induced within a week a rapid loss of 72% of Brn3a+RGCs, a transient downregulation of melanopsin expression (but not m+RGC death), and a thinning of the inner retinal layers.This study was supported by the Fundación Séneca, Agencia de Ciencia y Tecnología Región de Murcia (19881/GERM/15), and the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional “una manera de hacer Europa” (SAF2015-67643-P, PI16/00380, RD16/0008/0026 and RD16/0008/0016)

Tear and aqueous humour cytokine profile in primary open‐angle glaucoma

Purpose: To evaluate the concentrations of pro‐inflammatory cytokines in tear and aqueous humour of patients with primary open‐angle glaucoma (POAG), relative to healthy controls. Method: Tear and aqueous humour samples were collected from 29 healthy controls and 27 POAG patients. Twenty‐seven inflammatory cytokines were analysed: interleukin (IL)‐1β, IL‐1ra, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL9, IL‐10, IL‐12, IL‐13, IL‐15, IL‐17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony‐stimulating factor, granulocyte‐monocyte colony‐stimulating factor, interferon (IFN)‐γ, interferon gamma‐induced protein, monocyte chemo‐attractant protein‐1, macrophage inflammatory protein (MIP)‐1α, MIP‐1β, platelet‐derived growth factor, regulated on activation normal T cell expressed and secreted, tumour necrosis factor (TNF)‐α and vascular endothelial growth factor (VEGF). Results: In tear samples of glaucoma patients, an increase in IL‐4, IL‐12, IL‐15, FGF‐basic and VEGF was observed, as well as a decrease in MIP‐1a relative to the control group (p < 0.05). IL‐5, IL‐12, IL‐15, IFN‐γ and MIP‐1a were significantly higher in aqueous humour of glaucoma eyes (p < 0.05). A poor correlation between cytokine levels in tear and aqueous humour was observed. Conclusion: The different profiles of inflammatory marker expression of patients with POAG and healthy controls confirm the inflammatory activity of the pathology, indicating that some of them could be used as potential biomarkers of this disease

Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina

PurposeThe aim of this study was to investigate, the neuroprotective effects of a new Gramine derivative named: ITH12657, in a model of retinal excitotoxicity induced by intravitreal injection of NMDA.MethodsAdult Sprague Dawley rats received an intravitreal injection of 100 mM NMDA in their left eye and were treated daily with subcutaneous injections of ITH12657 or vehicle. The best dose–response, therapeutic window study, and optimal treatment duration of ITH12657 were studied. Based on the best survival of Brn3a + RGCs obtained from the above-mentioned studies, the protective effects of ITH12657 were studied in vivo (retinal thickness and full-field Electroretinography), and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs and their subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs.ResultsAdministration of 10 mg/kg ITH12657, starting 12 h before NMDA injection and dispensed for 3 days, resulted in the best significant protection of Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-treated rats showed significant preservation of retinal thickness and functional protection against NMDA-induced retinal excitotoxicity. Ex vivo results showed that ITH12657 afforded a significant protection against NMDA-induced excitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, but not for the population of αOFF-RGC, while the population of α-ONtRGC was fully resistant to NMDA-induced excitotoxicity.ConclusionSubcutaneous administration of ITH12657 at 10 mg/kg, initiated 12 h before NMDA-induced retinal injury and continued for 3 days, resulted in the best protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-induced RGC death. The population of αOFF-RGCs was extremely sensitive while α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity

Proinflammatory cytokine profile differences between primary open angle and pseudoexfoliative glaucoma

Introduction: Few studies have investigated glaucoma biomarkers in aqueous humor and tear and have found elevations of proinflammatory cytokines in patients with primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PXG). In this study we investigate differences in inflammatory cytokines between POAG and PXG patients to find specific disease biomarkers. Methods: For this purpose, tear and aqueous humor samples of 14 eyes with POAG and 15 eyes with PXG undergoing cataract surgery were immunoassayed for 27 pro-inflammatory cytokines. The concentrations of cytokines in tear and aqueous humor and their association with clinical variables were analysed, correlated and compared between the groups. Results: We found that the levels of three cytokines differed significantly in the aqueous humor of POAG and PXG patients: IL-12 and IL-13 were higher in the POAG group, while MCP-1(MCAF) was higher in the PXG group. The number of topical hypotensive medications was correlated with diminished levels of two cytokines (IL-7 and basic fibroblast growth factor) in aqueous humor in the POAG group and with diminished levels of IL-12 in tear in the PXG group. Conclusion: We conclude that both POAG and PXG show elevated concentrations of proinflammatory cytokines in tear and aqueous humor that could be used as biomarkers for these types of glaucoma and that the concentrations in aqueous humor of three cytokines: IL-12, IL-13 and MCP-1(MCAF) could be used to differentiate POAG and PXG

Implementation of a mindfulness-based crisis intervention for frontline healthcare workers during the COVID-19 outbreak in a public general hospital in Madrid, Spain

Introduction: The COVID-19 outbreak is having an impact on the well-being of healthcare workers. Mindfulness-based interventions have shown effectiveness in reducing stress and fostering resilience and recovery in healthcare workers. There are no studies examining the feasibility of brief mindfulness-based interventions during the COVID-19 outbreak. Materials and Methods: This is an exploratory study with a post intervention assessment. We describe an on-site brief mindfulness intervention and evaluate its helpfulness, safety, and feasibility. Results: One thousand out of 7,000 (14%) healthcare workers from La Paz University Hospital in Madrid (Spain) participated in at least one session. One hundred and fifty out of 1,000 (15%) participants filled out a self-report questionnaire evaluating the helpfulness of the intervention for on-site stress reduction. Ninety two subjects (61%) participated in more than one session. Most of the participants were women (80%) with a mean age of 38.6 years. Almost half of the sample were nurses (46%). Sessions were perceived as being helpful with a mean rating of 8.4 on a scale from 0 to 10. Only 3 people (2%) reported a minor adverse effect (increased anxiety or dizziness). Discussion: Our data supports the utility, safety and feasibility of an on-site, brief mindfulness-based intervention designed to reduce stress for frontline health workers during a crisis. There is a need to continue testing this type of interventions, and to integrate emotion regulation strategies as an essential part of health workers' general training. Clinical Trial Registration number: NCT04555005