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1.
Ophthalmic Res ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39079514

RESUMEN

INTRODUCTION: The purpose of this project was to explore the current standards of clinical care genetic testing and counseling for patients with inherited retinal diseases (IRDs) from the perspective of leading experts in selected European countries. Also, to gather opinions on current bottlenecks and future solutions to improve patient care. METHODS: On the initiative of the European Vision Institute, a survey questionnaire with 41 questions was designed and sent to experts in the field from ten European countries. Each participant was asked to answer with reference to the situation in their own country. RESULTS: Sixteen questionnaires were collected by November 2023. IRD genetic tests are performed in clinical care settings for 80% or more of tested patients in 9 countries, and the costs of genetic tests in clinical care are covered by the public health service to the extent of 90% or more in 8 countries. The median proportion of patients who are genetically tested, the median rate of genetically solved patients among those who are tested, and the median proportion of patients receiving counseling are 51-70%, 61-80% and 61-80%, respectively. Improving the education of healthcare professionals who facilitate patient referrals to specialised centres, improving access of patients to more thorough genotyping, and increasing the number of available counselors were the most advocated solutions. CONCLUSION: There is a significant proportion of IRD patients who are not genetically tested, whose genetic testing is inconclusive, or who do not receive counseling. Educational programs, greater availability of state-of-the-art genotyping and genetic counselors could improve healthcare for IRD patients.

2.
Case Rep Ophthalmol ; 15(1): 542-547, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015244

RESUMEN

Introduction: We aimed to describe a case of bilateral keratoconjunctivitis after exposure to the toxic sap of Euphorbia lathyris. Case Report: A 76-year-old gentleman presented after exposure to E. lathyris whilst he was gardening. He had 6/12 visual acuity in his right eye, and 6/4 in his left. Examination revealed marked periocular dermatitis, conjunctival injection and corneal oedema in the right eye with diffuse punctate epithelial staining. He was treated with ocular irrigation, topical steroids, antibiotics, cycloplegics and lubricants. Over 48 h, his left eye started to become symptomatic. He developed bilateral corneal epithelial defects and anterior chamber inflammation. His visual acuity worsened to 6/36 right and 6/24 left. At his 3-week follow-up, there was marked improvement in the resolution of the toxic keratoconjunctivitis in both eyes. Conclusion: Toxic sap from E. lathyris can cause severe keratoconjunctivitis. Irrigation of both eyes despite unilateral symptoms and early follow-up should be considered signs of toxicity may only become evident after 24-48 h.

3.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38612856

RESUMEN

PURPOSE: Resveratrol is a natural polyphenol which has a very low bioavailability but whose antioxidant, anti-inflammatory and anti-apoptotic properties may have therapeutic potential for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Previously, we reported the oral administration of resveratrol nanoparticles (RNs) elicited a neuroprotective effect in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, at significantly lower doses than unconjugated resveratrol (RSV) due to enhanced bioavailability. Furthermore, we demonstrated that the intranasal administration of a cell-derived secretome-based therapy at low concentrations leads to the selective neuroprotection of the optic nerve in EAE mice. The current study sought to assess the potential selective efficacy of lower concentrations of intranasal RNs for attenuating optic nerve damage in EAE mice. METHODS: EAE mice received either a daily intranasal vehicle, RNs or unconjugated resveratrol (RSV) for a period of thirty days beginning on the day of EAE induction. Mice were assessed daily for limb paralysis and weekly for visual function using the optokinetic response (OKR) by observers masked to treatment regimes. After sacrifice at day 30, spinal cords and optic nerves were stained to assess inflammation and demyelination, and retinas were immunostained to quantify retinal ganglion cell (RGC) survival. RESULTS: Intranasal RNs significantly increased RGC survival at half the dose previously shown to be required when given orally, reducing the risk of systemic side effects associated with prolonged use. Both intranasal RSV and RN therapies enhanced RGC survival trends, however, only the effects of intranasal RNs were significant. RGC loss was prevented even in the presence of inflammatory and demyelinating changes induced by EAE in optic nerves. CONCLUSIONS: The intranasal administration of RNs is able to reduce RGC loss independent of the inflammatory and demyelinating effects on the optic nerve and the spinal cord. The concentration of RNs needed to achieve neuroprotection is lower than previously demonstrated with oral administration, suggesting intranasal drug delivery combined with nanoparticle conjugation warrants further exploration as a potential neuroprotective strategy for the treatment of optic neuritis, alone as well as in combination with glucocorticoids.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Nanopartículas , Animales , Ratones , Resveratrol/farmacología , Neuroprotección , Administración Intranasal , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico
4.
Curr Med Res Opin ; 40(4): 647-655, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38410906

RESUMEN

OBJECTIVE: To evaluate the prevalence of comorbidities that may limit or prevent adherence to topical ocular hypotensive therapy in patients with open-angle glaucoma (OAG). METHODS: The UK Clinical Practice Research Datalink (CPRD) database of primary and secondary care and prescription records was analyzed to identify patients with a first (index) diagnosis of OAG during 2016-2020. The primary care records of these patients were screened for diagnostic terms linked to prespecified (qualifying) comorbidities considered to have the potential to impact patients' ability to instill eye drops. The prevalence of each of 10 categories of qualifying comorbidity recorded within the period from 5 years before to 2 years after the index OAG diagnosis was analyzed. RESULTS: A total of 100,968 patients with OAG were included in the analysis. Among the patients in the OAG cohort, 13,962 (13.8%) were aged 40-54 years, 32,145 (31.8%) were aged 55-69 years, 42,042 (41.6%) were aged 70-84 years, and 12,819 (12.7%) were aged 85+ years. Within the OAG population, 82.7%, 14.6%, and 2.7% of patients had no category, one category, and two or more categories of qualifying comorbidity, respectively. Qualifying comorbidities were most common in older patients. The most prevalent qualifying comorbidities were categorized as degenerative, traumatic, or pathological central nervous system disorder disrupting cognitive function (5.2%), movement disorder (4.4%), and low vision (4.1%). The prevalence of arthropathies and injuries affecting upper limbs (including arthritis in the hands) was 2.4%. CONCLUSIONS: The presence of comorbidities should be considered when determining whether eye drops are suitable treatment for glaucoma. Neurodegenerative disease affecting cognition and memory, motor disease, and low vision are common comorbidities that may impact adherence to eye drops, and affected patients may benefit from non-drop treatment modalities.


Asunto(s)
Glaucoma de Ángulo Abierto , Enfermedades Neurodegenerativas , Baja Visión , Humanos , Anciano , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/epidemiología , Presión Intraocular , Baja Visión/epidemiología , Prevalencia , Antihipertensivos/uso terapéutico , Comorbilidad , Soluciones Oftálmicas/uso terapéutico
5.
Eur J Ophthalmol ; 34(1): 204-216, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37097882

RESUMEN

PURPOSE: To investigate the impact of the delay in patient appointments caused by the COVID-19 pandemic and the triage system on the glaucomatous disease of patients in a London tertiary hospital. METHODS: Observational retrospective study that randomly selected 200 glaucoma patients with more than 3 months of unintended delay for their post-COVID visit and other inclusion and exclusion criteria. Demographic information, clinical data, number of drugs, best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) mean deviation (MD), and global peripapillary retinal nerve fibre layer (pRNFL) thickness were obtained from the pre- and post-COVID visit. At the post-COVID visit, the clinical outcomes subjective clinical concern and change of treatment or need for surgery were also annotated. The variables were stratified by glaucoma severity (according to the MD into early, moderate and advanced) and by delay time (more and less than 12 months) and analysed using SPSS. RESULTS: We included 121 eyes (from 71 patients). The median patient age was 74 years (interquartile range -IQR- 15), 54% were males and 52% Caucasians. Different glaucoma types and all glaucoma severities were included. When data was stratified for glaucoma severity, at the pre-COVID visit, significant differences in BCVA, CCT and IOP were observed and there were significantly higher values in the early glaucoma group. The median follow-up delay was 11 months (IQR 8), did not differ between the glaucoma severity groups and did not correlate to the glaucoma severity. At the post-COVID visit, significant differences in BCVA, IOP, and Global pRNFL thickness were observed between the glaucoma severity groups, as lower BCVA and higher IOP and pRNFL thickness were observed in the early glaucoma group. At the post-COVID visit there was cause for concern in 40 eyes: 5 were followed more closely, 22 had a change of treatment and 13 were booked for surgery (3 for cataract and 10 for glaucoma surgery). However, the number of eyes with causes for concern were similar between the glaucoma severity groups and there was no correlation between these clinical outcomes and the delay of the post-COVID visit. The number of topical hypotensive medications increased significantly after the post-COVID visit, higher number of medications were observed in the advanced glaucoma group. When differences of IOP, MD and pRNFL thickness between the pre and post-COVID visit, only the MD difference was significantly different between the glaucoma severity groups because it was higher in the severe group. When data was stratified for delay longer or shorter than 12 months, no differences were observed between the groups except at the pre-COVID visit, when the numbers of patients with MD deviation >-6 dB had longer delay time. When differences in IOP, MD and RNFL thickness were calculated, only the pRNFL thickness showed significant differences between the delay groups, because it was higher in the longer delay group. Finally, when paired analysis of the variables at the pre- and post-COVID visits, stratified by glaucoma severity and delay were conducted, although there were no significant differences in IOP in any group, the BCVA decreased significantly in the overall group and in the longer delay groups, the number of hypotensive drugs increased significantly overall and in the moderate and advanced glaucoma, the MD of the VF worsened significantly in the overall group and in the early glaucoma and longer delay groups and the pRNFL thickness decreased significantly in all groups. CONCLUSIONS: We document that delayed care impacts negatively on the glaucomatous disease of our patients because at the post-COVID visit there were reasons for clinical concern in a third of eyes that resulted in change of treatment or surgery. However, these clinical consequences were not related to IOP, glaucoma severity or delay time and reflect that the triage methods implemented worked adequately. The most sensitive parameter to indicate progression in our sample was the pRNFL thickness.


Asunto(s)
COVID-19 , Glaucoma , Masculino , Humanos , Anciano , Femenino , Estudios Retrospectivos , Londres/epidemiología , Pandemias , Centros de Atención Terciaria , COVID-19/epidemiología , Glaucoma/epidemiología , Glaucoma/cirugía , Presión Intraocular
6.
Neurotherapeutics ; 20(4): 1138-1153, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37160530

RESUMEN

Resveratrol is a natural polyphenol which may be useful for treating neurodegenerative diseases such as multiple sclerosis (MS). To date, current immunomodulatory treatments for MS aim to reduce inflammation with limited effects on the neurodegenerative component of this disease. The purpose of the current study is to develop a novel nanoparticle formulation of resveratrol to increase its solubility, and to assess its ability to prevent optic nerve and spinal cord degeneration in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Resveratrol nanoparticles (RNs) were made using a thin rehydration technique. EAE mice received a daily oral administration of vehicle, RNs or unconjugated resveratrol for one month. They were assessed daily for clinical signs of paralysis and weekly for their visual acuity with optokinetic responses (OKR). After one month, their spinal cords and optic nerves were stained for inflammation and demyelination and retinal ganglion cells immunostained for Brn3a. RNs were stable for three months. The administration of RNs did not have any effect on clinical manifestation of EAE and did not preserve OKR scores but reduced the intensity of the disease. It did not reduce inflammation and demyelination in the spinal cord and the optic nerve. However, RNs were able to decrease RGC loss compared to the vehicle. Results demonstrate that resveratrol is neuroprotective by reducing RGC loss. Interestingly, neuroprotective effects and decreased disease severity occurred without reduction of inflammation or demyelination, suggesting this therapy may fill an unmet need to limit the neurodegenerative component of MS.


Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Fármacos Neuroprotectores , Neuritis Óptica , Ratones , Animales , Resveratrol , Fármacos Neuroprotectores/uso terapéutico , Solubilidad , Ratones Endogámicos C57BL , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Modelos Animales de Enfermedad
7.
Lab Chip ; 22(18): 3521-3532, 2022 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-35979801

RESUMEN

Glaucoma, a ruinous group of eye diseases with progressive degeneration of the optic nerve and vision loss, is the leading cause of irreversible blindness. Accurate and timely diagnosis of glaucoma is critical to promote secondary prevention and early disease-modifying therapies. Reliable, cheap, and rapid tests for measuring disease activities are highly required. Brain-derived neurotrophic factor (BDNF) plays an important role in maintaining the function and survival of the central nervous system. Decreased BDNF levels in tear fluid can be seen in glaucoma patients, which indicates that BDNF can be regarded as a novel biomarker for glaucoma. Conventional ELISA is the standard method to measure the BDNF level, but the multi-step operation and strict storage conditions limit its usage in point-of-care settings. Herein, a one-step and a portable glaucoma detection method was developed based on the lateral flow assay (LFA) to quantify the BDNF concentration in artificial tear fluids. The results of the LFA were analyzed by using a portable and low-cost system consisting of a smartphone camera and a dark readout box fabricated by 3D printing. The concentration of BDNF was quantified by analyzing the colorimetric intensity of the test line and the control line. This assay yields reliable quantitative results from 25 to 300 pg mL-1 with an experimental detection limit of 14.12 pg mL-1. The LFA shows a high selectivity for BDNF and high stability in different pH environments. It can be readily adapted for sensitive and quantitative testing of BDNF in a point-of-care setting. The BDNF LFA strip shows it has great potential to be used in early glaucoma detection.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Glaucoma , Glaucoma/diagnóstico , Humanos , Sistemas de Atención de Punto , Células Ganglionares de la Retina
8.
Ophthalmol Glaucoma ; 5(6): 562-571, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35714909

RESUMEN

PURPOSE: To evaluate the novel Rose Plot Analysis (RPA) in the analysis and presentation of glaucoma structural progression data. DESIGN: Case-control image analysis study using retrospective retinal imaging series. SUBJECTS: Subjects with open-angle glaucoma with at least 5 registered spectral-domain OCT scans. METHODS: Glaucoma RPA was developed, combining a novel application of angular histograms and dynamic cluster analysis of circumpapillary retinal nerve fiber layer (cRNFL) OCT data. Rose Plot Analysis plots were created for each eye and each visit. Significant clusters of progression were indicated in red. Three masked clinicians categorized all RPA plots (progressing, not progressing), in addition to measuring the significant RPA area. A masked OCT series assessment with linear regression of averaged global and sectoral cRNFL thicknesses was conducted as the clinical imaging standard. MAIN OUTCOME MEASURES: Interobserver agreement was compared between RPA and the clinical imaging standard. Discriminative ability was assessed using receiver-operating characteristic curves. The time to detection of progression was compared using a Kaplan-Meier survival analysis, and the agreement of RPA with the clinical imaging standard was calculated. RESULTS: Seven hundred fourty-three scans from 98 eyes were included. Interobserver agreement was significantly greater when categorizing RPA (κ, 0.86; 95% confidence interval [CI], 0.81-0.91) compared with OCT image series (κ, 0.66; 95% CI, 0.54-0.77). The discriminative power of RPA to differentiate between eyes that were progressing and not progressing (area under the curve [AUC], 0.97; 95% CI, 0.92-1.00) was greater than that of global cRNFL thickness (AUC, 0.71; 95% CI, 0.59-0.82; P < 0.0001) and equivalent to that of sectoral cRNFL regression (AUC, 0.97; 95% CI, 0.92-1.00). A Kaplan-Meier survival analysis showed that progression was detected 8.7 months sooner by RPA than by global cRNFL linear regression (P < 0.0001) in progressing eyes but was not sooner than with sectoral cRNFL (P = 0.06). Rose Plot Analysis showed substantial agreement with the presence of significant thinning on sectoral cRNFL linear regression (κ, 0.715; 95% CI, 0.578-0.853). CONCLUSIONS: Rose Plot Analysis has been shown to provide accurate and intuitive, at-a-glance data analysis and presentation that improve interobserver agreement and may aid early diagnosis of glaucomatous disease progression.


Asunto(s)
Glaucoma de Ángulo Abierto , Glaucoma , Disco Óptico , Enfermedades del Nervio Óptico , Rosa , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Fibras Nerviosas , Células Ganglionares de la Retina , Enfermedades del Nervio Óptico/diagnóstico , Presión Intraocular , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Glaucoma/diagnóstico , Análisis por Conglomerados
9.
Front Cell Neurosci ; 16: 804782, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35370560

RESUMEN

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.

10.
Biosens Bioelectron ; 196: 113700, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34653715

RESUMEN

Glaucoma is the leading cause of irreversible blindness globally which significantly affects the quality of life and has a substantial economic impact. Effective detective methods are necessary to identify glaucoma as early as possible. Regular eye examinations are important for detecting the disease early and preventing deterioration of vision and quality of life. Current methods of measuring disease activity are powerful in describing the functional and structural changes in glaucomatous eyes. However, there is still a need for a novel tool to detect glaucoma earlier and more accurately. Tear fluid biomarker analysis and new imaging technology provide novel surrogate endpoints of glaucoma. Artificial intelligence is a post-diagnostic tool that can analyse ophthalmic test results. A detail review of currently used clinical tests in glaucoma include intraocular pressure test, visual field test and optical coherence tomography are presented. The advanced technologies for glaucoma measurement which can identify specific disease characteristics, as well as the mechanism, performance and future perspectives of these devices are highlighted. Applications of AI in diagnosis and prediction in glaucoma are mentioned. With the development in imaging tools, sensor technologies and artificial intelligence, diagnostic evaluation of glaucoma must assess more variables to facilitate earlier diagnosis and management in the future.


Asunto(s)
Técnicas Biosensibles , Glaucoma , Inteligencia Artificial , Glaucoma/diagnóstico , Humanos , Calidad de Vida , Pruebas del Campo Visual
11.
Analyst ; 146(21): 6416-6444, 2021 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-34591045

RESUMEN

Point-of-care diagnosis and personalized treatments are critical in ocular physiology and disease. Continuous sampling of tear fluid for ocular diagnosis is a need for further exploration. Several techniques have been developed for possible ophthalmological applications, from traditional spectroscopies to wearable sensors. Contact lenses are commonly used devices for vision correction, as well as for other therapeutic and cosmetic purposes. They are increasingly being developed into ocular sensors, being used to sense and monitor biochemical analytes in tear fluid, ocular surface temperature, intraocular pressure, and pH value. These sensors have had success in detecting ocular conditions, optimizing pharmaceutical treatments, and tracking treatment efficacy in point-of-care settings. However, there is a paucity of new and effective instrumentation reported in ophthalmology. Hence, this review will summarize the applied ophthalmic technologies for ocular diagnostics and tear monitoring, including both conventional and biosensing technologies. Besides applications of smart readout devices for continuous monitoring, targeted biomarkers are also discussed for the convenience of diagnosis of various ocular diseases. A further discussion is also provided for future aspects and market requirements related to the commercialization of novel types of contact lens sensors.


Asunto(s)
Técnicas Biosensibles , Lentes de Contacto , Oftalmopatías , Oftalmopatías/diagnóstico , Humanos , Monitoreo Fisiológico , Lágrimas
12.
Adv Protein Chem Struct Biol ; 126: 279-306, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34090617

RESUMEN

Apoptosis is a form of programmed cell death (PCD) and enables the immunologically silent disposal of senescent or unwanted cells, causing minimal damage to the surrounding environment. Apoptosis can occur via intrinsic or extrinsic pathways that initiate a series of intracellular and extracellular signaling events. This ultimately leads to the clearance of the cell by phagocytes. This normal physiological mechanism may be accelerated in several diseases including those involving the eyes and brain, leading to loss of structure and function. This review presents the role of PCD in the health of the eyes and brain, and the evidence presented for its aberrant role in disease.


Asunto(s)
Apoptosis , Encefalopatías/metabolismo , Oftalmopatías/metabolismo , Transducción de Señal , Animales , Humanos
13.
Curr Alzheimer Res ; 18(2): 89-102, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33855942

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disorder, the most common form of dementia. AD is characterised by amyloid-ß (Aß) plaques and neurofibrillary tangles (NFT) in the brain, in association with neuronal loss and synaptic failure, causing cognitive deficits. Accurate and early diagnosis is currently unavailable in lifespan, hampering early intervention of potential new treatments. Visual deficits have been well documented in AD patients, and the pathological changes identified in the brain are also believed to be found in the retina, an integral part of the central nervous system. Retinal changes can be detected by real-time non-invasive imaging, due to the transparent nature of the ocular media, potentially allowing an earlier diagnosis as well as monitoring disease progression and treatment outcome. Animal models are essential for AD research, and this review has a focus on retinal changes in various transgenic AD mouse models with retinal imaging and immunohistochemical analysis as well as therapeutic effects in those models. We also discuss the limitations of transgenic AD models in clinical translations.


Asunto(s)
Enfermedad de Alzheimer/patología , Modelos Animales de Enfermedad , Inmunohistoquímica , Ratones Transgénicos , Retina/patología , Péptidos beta-Amiloides/metabolismo , Animales , Ratones , Ovillos Neurofibrilares/patología , Placa Amiloide/patología , Proteínas tau/metabolismo
15.
Expert Opin Investig Drugs ; 30(5): 571-577, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33641585

RESUMEN

INTRODUCTION: Retinal neurodegeneration causes irreversible vision loss, impairing quality of life. By targeting neurotoxic conditions, such as oxidative stress and ischemia, neuroprotectants can slow or stop sight loss resulting from eye disease. Despite limimted clinical use of neuroprotectants, there are several promising compounds in early clinical trials (pre-phase III) which may fulfil new therapeutic roles. Search terms relating to neuroprotection and eye disease were used on ClinicalTrials.gov to identify neuroprotective candidates. AREAS COVERED: Research supporting neuroprotection in eye diseases is focused on, ranging from preclinical to phase II, according to the ClinicalTrials.gov database. The compounds discussed are explored in terms of future clinical applications. EXPERT OPINION: The major challenge in neuroprotection research is translation from basic research to the clinic. A number of potential neuroprotectants have progressed to ophthalmology clinical trials in recent years, with defined mechanisms of action - saffron and CoQ10 - targeting mitochondria, and both CNTF and NGF showing anti-apoptotic effects. Enhancements in trial design and patient cohorts in proof-of-concept trials with enriched patient populations and surrogate endpoints should accelerate drug development. A further important consideration is optimising drug delivery to improve individualised management and patient compliance. Progress in these areas means that neuroprotective strategies have a much improved chance of translational success.


Asunto(s)
Desarrollo de Medicamentos , Fármacos Neuroprotectores/farmacología , Enfermedades de la Retina/tratamiento farmacológico , Animales , Sistemas de Liberación de Medicamentos , Drogas en Investigación/administración & dosificación , Drogas en Investigación/farmacología , Humanos , Fármacos Neuroprotectores/administración & dosificación , Calidad de Vida , Proyectos de Investigación , Enfermedades de la Retina/fisiopatología
16.
Alzheimers Dement ; 17(1): 103-111, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33090722

RESUMEN

In the last 20 years, research focused on developing retinal imaging as a source of potential biomarkers for Alzheimer's disease and other neurodegenerative diseases, has increased significantly. The Alzheimer's Association and the Alzheimer's & Dementia: Diagnosis, Assessment, Disease Monitoring editorial team (companion journal to Alzheimer's & Dementia) convened an interdisciplinary discussion in 2019 to identify a path to expedite the development of retinal biomarkers capable of identifying biological changes associated with AD, and for tracking progression of disease severity over time. As different retinal imaging modalities provide different types of structural and/or functional information, the discussion reflected on these modalities and their respective strengths and weaknesses. Discussion further focused on the importance of defining the context of use to help guide the development of retinal biomarkers. Moving from research to context of use, and ultimately to clinical evaluation, this article outlines ongoing retinal imaging research today in Alzheimer's and other brain diseases, including a discussion of future directions for this area of study.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedades Neurodegenerativas/diagnóstico por imagen , Retina/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Biomarcadores , Encéfalo/diagnóstico por imagen , Humanos , Persona de Mediana Edad
17.
Ophthalmologica ; 244(5): 408-417, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33279894

RESUMEN

The transparent eye media represent a window through which to observe changes occurring in the retina during pathological processes. In contrast to visualising the extent of neurodegenerative damage that has already occurred, imaging an active process such as apoptosis has the potential to report on disease progression and therefore the threat of irreversible functional loss in various eye and brain diseases. Early diagnosis in these conditions is an important unmet clinical need to avoid or delay irreversible sight loss. In this setting, apoptosis detection is a promising strategy with which to diagnose, provide prognosis and monitor therapeutic response. Additionally, monitoring apoptosis in vitro and in vivo has been shown to be valuable for drug development in order to assess the efficacy of novel therapeutic strategies both in the pre-clinical and clinical setting. Detection of Apoptosing Retinal Cells (DARC) technology is to date the only tool of its kind to have been tested in clinical trials, with other new imaging techniques under investigation in the fields of neuroscience, ophthalmology and drug development. We summarise the transitioning of techniques detecting apoptosis from bench to bedside, along with the future possibilities they encase.


Asunto(s)
Glaucoma , Células Ganglionares de la Retina , Apoptosis , Diagnóstico por Imagen , Humanos , Retina
18.
Sci Rep ; 10(1): 21683, 2020 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-33303775

RESUMEN

Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.


Asunto(s)
Tamaño de la Célula , Enfermedades del Nervio Óptico/patología , Retina/citología , Retina/patología , Células Ganglionares de la Retina/patología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/etiología , Ratas Endogámicas Dahl
19.
Int J Mol Sci ; 21(23)2020 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-33291255

RESUMEN

Coenzyme Q10 (CoQ10) is a ubiquitous cofactor in the body, operating in the inner mitochondrial membrane, where it plays a vital role in the generation of adenosine triphosphate (ATP) through the electron transport chain (ETC). In addition to this, CoQ10 serves as an antioxidant, protecting the cell from oxidative stress by reactive oxygen species (ROS) as well as maintaining a proton (H+) gradient across lysosome membranes to facilitate the breakdown of cellular waste products. Through the process of ageing, the body becomes deficient in CoQ10, resulting in several systemic manifestations. On a cellular level, one of the consequences of CoQ10 deficiency is apoptosis, which can be visualised in tissues of the central nervous system (CNS). Diseases affecting the retina and brain such as age-related macular degeneration (AMD), glaucoma, Alzheimer's disease (AD) and Parkinson's disease (PD) have shown defects in cellular biochemical reactions attributed to reduced levels of CoQ10. Through further research into the pathogenesis of such conditions, the effects of CoQ10 deficiency can be counteracted through supplementation, early detection and intervention.


Asunto(s)
Ataxia/metabolismo , Encéfalo/metabolismo , Enfermedades Mitocondriales/metabolismo , Debilidad Muscular/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Retina/metabolismo , Ubiquinona/deficiencia , Animales , Ataxia/complicaciones , Ataxia/patología , Encéfalo/patología , Humanos , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/patología , Debilidad Muscular/complicaciones , Debilidad Muscular/patología , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/patología , Retina/patología , Ubiquinona/análogos & derivados , Ubiquinona/metabolismo
20.
Expert Rev Med Devices ; 17(10): 1095-1108, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32885710

RESUMEN

INTRODUCTION: Retinal imaging is a key investigation in ophthalmology. New devices continue to be created to keep up with the demand for better imaging modalities in this field. This review looks to highlight current trends and the future of retinal imaging. AREAS COVERED: This review looks at the advances in topographical imaging, photoacoustic microscopy, optical coherence tomography and molecular imaging. There is future scoping on further advances in retinal imaging. EXPERT OPINION: Retinal imaging continues to develop at a rapid pace to improve diagnosis and management of patients. We will see the development of big data to gain powerful insights and new technologies such as teleophthalmology mature in the future.


Asunto(s)
Imagenología Tridimensional/tendencias , Enfermedades de la Retina/diagnóstico por imagen , Angiografía , Fondo de Ojo , Humanos , Oftalmoscopía , Tomografía de Coherencia Óptica
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