scholarly journals The primate model for understanding and restoring vision

2019 ◽  
Vol 116 (52) ◽  
pp. 26280-26287 ◽  
Author(s):  
Serge Picaud ◽  
Deniz Dalkara ◽  
Katia Marazova ◽  
Olivier Goureau ◽  
Botond Roska ◽  
...  
Keyword(s):  
Vision Loss ◽  
Basic Research ◽  
Human Vision ◽  
Biological Mechanisms ◽  
Primate Model ◽  
Retinal Dystrophies ◽  
Age Related ◽  
High Acuity ◽  
Research Findings ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases caused by photoreceptor cell death are major causes of irreversible vision loss. As only primates have a macula, the nonhuman primate (NHP) models have a crucial role not only in revealing biological mechanisms underlying high-acuity vision but also in the development of therapies. Successful translation of basic research findings into clinical trials and, moreover, approval of the first therapies for blinding inherited and age-related retinal dystrophies has been reported in recent years. This article explores the value of the NHP models in understanding human vision and reviews their contribution to the development of innovative therapeutic strategies to save and restore vision.

scholarly journals Contribution of Microglia-Mediated Neuroinflammation to Retinal Degenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Maria H. Madeira ◽  
Raquel Boia ◽  
Paulo F. Santos ◽  
António F. Ambrósio ◽  
Ana R. Santiago
Keyword(s):  
Vision Loss ◽  
Neuronal Loss ◽  
Age Related Macular Degeneration ◽  
Therapeutic Interventions ◽  
Degenerative Diseases ◽  
Disease Etiology ◽  
Neurodegenerative Process ◽  
Age Related ◽  
Retinal Microglia ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

scholarly journals Simulated central vision loss impairs implicit location probability learning

2020 ◽  
Author(s):  
Douglas A Addleman ◽  
Gordon E Legge ◽  
Yuhong Jiang
Keyword(s):  
Vision Loss ◽  
Target Location ◽  
Probability Learning ◽  
Age Related Macular Degeneration ◽  
Oculomotor Control ◽  
Central Scotoma ◽  
Central Vision ◽  
Central Vision Loss ◽  
Age Related ◽  
High Acuity

Central vision loss (CVL) occurs in advanced forms of age-related macular degeneration (AMD). It impairs high-acuity vision and results in difficulties with oculomotor control. Goal-driven guidance of attention is less effective in people with CVL, but do central scotomas also affect implicit, experience-driven attention? We investigated how simulated central scotomas affect young adults’ ability to prioritize locations that frequently contain a visual search target (location probability learning). Experiment 1 successfully induced probability learning in a no scotoma phase, regardless of whether participants became aware of the target’s location probability. Subsequently, central scotomas were introduced using a gaze-contingent eye tracking paradigm. The previously learned spatial bias persisted for a short time in this phase, an effect that was statistically comparable for no-scotoma and scotoma testing. Experiment 2 investigated whether participants could acquire location probability learning when trained with a simulated central scotoma. Unlike Experiment 1, training with a central scotoma yielded location probability learning only in participants who were aware of the target’s location probability. This effect transferred to search with no scotoma in aware but not unaware participants. Together, the results show that simulated central vision loss interferes with the acquisition of implicitly learned location probability learning, supporting a role of central vision in implicit spatial attentional biases.

scholarly journals The Role of Inflammation in Retinal Neurodegeneration and Degenerative Diseases

2021 ◽  
Vol 23 (1) ◽  
pp. 386
Author(s):  
Geetika Kaur ◽  
Nikhlesh K. Singh
Keyword(s):  
Retinal Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Treatment Modalities ◽  
Macular Dystrophy ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Neurodegeneration ◽  
Retinal Degenerative Diseases

Retinal neurodegeneration is predominantly reported as the apoptosis or impaired function of the photoreceptors. Retinal degeneration is a major causative factor of irreversible vision loss leading to blindness. In recent years, retinal degenerative diseases have been investigated and many genes and genetic defects have been elucidated by many of the causative factors. An enormous amount of research has been performed to determine the pathogenesis of retinal degenerative conditions and to formulate the treatment modalities that are the critical requirements in this current scenario. Encouraging results have been obtained using gene therapy. We provide a narrative review of the various studies performed to date on the role of inflammation in human retinal degenerative diseases such as age-related macular degeneration, inherited retinal dystrophies, retinitis pigmentosa, Stargardt macular dystrophy, and Leber congenital amaurosis. In addition, we have highlighted the pivotal role of various inflammatory mechanisms in the progress of retinal degeneration. This review also offers an assessment of various therapeutic approaches, including gene-therapies and stem-cell-based therapies, for degenerative retinal diseases.

Translational Research in Ophthalmology – A European Perspective

2011 ◽  
Vol 05 (01) ◽  
pp. 13
Author(s):  
José Cunha-Vaz ◽  
Eberhart Zrenner ◽  
◽  
◽  
◽  
...  
Keyword(s):  
Clinical Research ◽  
Translational Research ◽  
Basic Research ◽  
Age Related Macular Degeneration ◽  
Research Network ◽  
Clinical Research Network ◽  
Adequate Funding ◽  
Retinal Dystrophies ◽  
Age Related ◽  
Exogenous Factors

Loss of vision is a major threat for the ageing European society as its incidence quickly increases with age. While cataract is handled well by microsurgery, other blinding conditions such as age-related macular degeneration, retinal dystrophies, glaucoma and diabetic retinopathy cannot be treated well. On the other hand, knowledge about endogenous and exogenous factors increases rapidly in basic research, opening new pathways to therapy. It will be increasingly important to foster translational research to bring such new strategies in genetics, proteomics, metabolomics and new drug delivery systems for neuroprotection, stem cell research and optogenetics from bench to bedside. Adequate funding for this translational research has to be ensured. These goals are strongly supported by the European Vision Institute (EVI) and by the European Vision Institute Clinical Research Network (EVICR.net), a clinical research network that comprises more than 70 certified sites to perform clinical studies in the field of ophthalmology and by the European Clinical Research Infrastructures Network (ECRIN). These developments, their aims and accomplishments are described here.

scholarly journals Bestrophinopathies: perspectives on clinical disease, Bestrophin-1 function and developing therapies

2021 ◽  
Vol 13 ◽  
pp. 251584142199719
Author(s):  
Simranjeet Singh Grewal ◽  
Joseph J. Smith ◽  
Amanda-Jayne F. Carr
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
Underlying Disease ◽  
Incomplete Penetrance ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
High Acuity ◽  
Induced Pluripotent

Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that typically affect the macular region, an area synonymous with central high acuity vision. This spectrum of disorders is caused by mutations in bestrophin1 ( BEST1), a protein thought to act as a Ca2+-activated Cl- channel in the retinal pigment epithelium (RPE) of the eye. Although bestrophinopathies are rare, over 250 individual pathological mutations have been identified in the BEST1 gene, with many reported to have various clinical expressivity and incomplete penetrance. With no current clinical treatments available for patients with bestrophinopathies, understanding the role of BEST1 in cells and the pathological pathways underlying disease has become a priority. Induced pluripotent stem cell (iPSC) technology is helping to uncover disease mechanisms and develop treatments for RPE diseases, like bestrophinopathies. Here, we provide a comprehensive review of the pathophysiology of bestrophinopathies and highlight how patient-derived iPSC-RPE are being used to test new genomic therapies in vitro.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

scholarly journals Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yamin Li ◽  
Lina Liang ◽  
Torkel Snellingen ◽  
Kai Xu ◽  
Yun Gao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Case Report Form ◽  
Link Type ◽  
Anti Vegf ◽  
Age Related ◽  
Function Test

Abstract Background Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. Methods/design This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. Discussion Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.

scholarly journals One-year outcomes of fixed-dosing Aflibercept therapy for pre treated and naive polypoidal choroidal vasculopathy patient

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hun Gu Choo ◽  
Jin Hae Lee ◽  
Hyun Sub Oh ◽  
Soon Hyun Kim ◽  
Yong Sung You ◽  
...  
Keyword(s):  
Polypoidal Choroidal Vasculopathy ◽  
Vision Loss ◽  
Case Series ◽  
Age Related Macular Degeneration ◽  
Research Information ◽  
Age Related ◽  
Case Series Study ◽  
Treatment Naïve ◽  
One Year ◽  
Choroidal Vasculopathy

Abstract Background Polypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration that can cause permanent vision loss. The purpose of this paper was to report the one-year outcomes of fixed-dosing aflibercept therapy for the treatment of PCV. Methods This was a prospective, single-arm, interventional case series study of 25 PCV patients; 12 pre-treated and 13 treatment-naïve patients. The patients were treated and monitored for 12 months. Each patient was administered with an aflibercept (2.0 mg) injection every month for the first 3 months (the loading phase), and thereafter, once every 2 months. At every follow-up visit, best-corrected visual acuity (BCVA) test, fundus examination, and optical coherence tomography for measuring the central subfield macular thickness (CSMT) were performed. Fluorescein and indocyanine green angiography were conducted at baseline and at 4 and 12 months. Results After 12 months of aflibercept therapy, the mean BCVA of the patients significantly improved from 65.48 letters at baseline to 69.91 letters (p=0.001), and the CSMT significantly decreased from 406.92 um at baseline to 276.12 um (p< 0.001). Additionally, ten patients (40%) showed complete polyp regression. The treatment-naïve patients showed a statistically significant improvement in BCVA from 66.58 letters at baseline to 76.36 letters at 12 months, and a significant decrease in CSMT, from 462 to 243 um. In the pre-treated group, there was no change in BCVA (64.46 letters), and the decrease in CSMT from 356.08 to 303.69 um was not statistically significant. Conclusions The fixed-dosing aflibercept regimen is effective for treating patients with PCV and is more effective in treatment-naïve patients than in pre-treated patients. Trial registration Clinical Research Information Service (CRiS), Republic of Korea. Identifer: KCT0005798, Registered: Jan 20, 2021. Retrospectively registered, URL: https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=18546

scholarly journals A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2441
Author(s):  
Drake W. Lem ◽  
Dennis L. Gierhart ◽  
Pinakin Gunvant Davey
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Microvascular Disease ◽  
Age Related Macular Degeneration ◽  
Cell Degeneration ◽  
Neuroprotective Effects ◽  
Age Related ◽  
Induced Changes ◽  
Dietary Carotenoid

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

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