scholarly journals Small-Molecule Modulation of PPARs for the Treatment of Prevalent Vascular Retinal Diseases

2020 ◽  
Vol 21 (23) ◽  
pp. 9251
Author(s):  
Xiaozheng Dou ◽  
Adam S. Duerfeldt
Keyword(s):  
Small Molecule ◽  
Treatment Strategies ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Peroxisome Proliferator ◽  
Retinal Diseases ◽  
Age Related ◽  
Ligand Discovery ◽  
Ppar Ligand ◽  
Peroxisome Proliferator Activated Receptors

Vascular-related retinal diseases dramatically impact quality of life and create a substantial burden on the healthcare system. Age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity are leading causes of irreversible blindness. In recent years, the scientific community has made great progress in understanding the pathology of these diseases and recent discoveries have identified promising new treatment strategies. Specifically, compelling biochemical and clinical evidence is arising that small-molecule modulation of peroxisome proliferator-activated receptors (PPARs) represents a promising approach to simultaneously address many of the pathological drivers of these vascular-related retinal diseases. This has excited academic and pharmaceutical researchers towards developing new and potent PPAR ligands. This review highlights recent developments in PPAR ligand discovery and discusses the downstream effects of targeting PPARs as a therapeutic approach to treating retinal vascular diseases.

scholarly journals PPAR-αLigands as Potential Therapeutic Agents for Wet Age-Related Macular Degeneration

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Marisol del V Cano ◽  
Peter L. Gehlbach
Keyword(s):  
Macular Degeneration ◽  
Immune Modulation ◽  
Age Related Macular Degeneration ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Age Related ◽  
Dry Amd ◽  
Peroxisome Proliferator Activated Receptors ◽  
Endothelial Growth Factor ◽  
Wet Amd

The peroxisome proliferator-activated receptors (PPAR's) are members of the steroid/thyroid nuclear receptor, superfamily of transcription factors. There are currently three known PPAR subtypes,α,β, andγ. The PPARs are now recognized participants in a number of biological pathways some of which are implicated in the pathogenesis of age-related macular degeneration (AMD). These include immune modulation, lipid regulation, and oxidant/antioxidant pathways important to the onset and progression of “dry” AMD, and vascular endothelial growth factor (VEGF) mediated pathways that stimulate choroidal neovascularization (CNV), characteristic of “wet” AMD. PPAR-αis found in retina and also on vascular cells important to formation of CNV. At this time, however, relatively little is known about potential contributions of PPAR-αto the pathogenesis of dry and wet AMD. This review examines current literature for potential roles of PPAR-αin the pathogenesis and potential treatment of AMD with emphasis on prevention and treatment of wet AMD.

scholarly journals Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1049
Author(s):  
Josh O. Wallsh ◽  
Ron P. Gallemore
Keyword(s):  
Treatment Options ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Vascular Endothelial ◽  
Future Directions ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Topical Medications

Anti-vascular endothelial growth factor (anti-VEGF) therapy currently plays a central role in the treatment of numerous retinal diseases, most notably exudative age-related macular degeneration (eAMD), diabetic retinopathy and retinal vein occlusions. While offering significant functional and anatomic benefits in most patients, there exists a subset of 15–40% of eyes that fail to respond or only partially respond. For these cases, various treatment options have been explored with a range of outcomes. These options include steroid injections, laser treatment (both thermal therapy for retinal vascular diseases and photodynamic therapy for eAMD), abbreviated anti-VEGF treatment intervals, switching anti-VEGF agents and topical medications. In this article, we review the effectiveness of these treatment options along with a discussion of the current research into future directions for anti-VEGF-resistant eyes.

scholarly journals Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases

2021 ◽  
Vol 11 (5) ◽  
pp. 321
Author(s):  
Kyoung Min Kim ◽  
Tae-Young Heo ◽  
Aesul Kim ◽  
Joohee Kim ◽  
Kyu Jin Han ◽  
...  
Keyword(s):  
Network Models ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Diagnostic Tools ◽  
Retinal Images ◽  
Dense Layer ◽  
Retinal Diseases ◽  
Fundus Image ◽  
Neural Network Models ◽  
Age Related

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist’s performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

scholarly journals Review of Subthreshold Diode Micropulse Laser Treatment for Retinal Diseases

2018 ◽  
Vol 1 (1) ◽  
pp. 62-70
Author(s):  
Juhn AT ◽  
Shyu AP ◽  
Benjamin J ◽  
Zhang Y
Keyword(s):  
Diabetic Retinopathy ◽  
Treatment Modality ◽  
Branch Retinal Vein Occlusion ◽  
Age Related Macular Degeneration ◽  
Clinical Settings ◽  
Retinal Diseases ◽  
Micropulse Laser ◽  
Vein Occlusion ◽  
Age Related ◽  
New Treatment

Subthreshold Diode Micropulse (SDM) laser is a relatively new treatment modality that confers very little to no anatomical risk to the retina. However, its efficacy is still being studied, and the scenario where SDM is most useful is still being elucidated. This paper reviews articles from 1997 to 2017 and reviews the settings, results, and outcomes of SDM in various clinical settings including diabetic macular edema, branch retinal vein occlusion, central serous Chorioretinopathy, proliferative diabetic retinopathy, and age-related macular degeneration.

scholarly journals Antioxidant Role of PRGF on RPE Cells after Blue Light Insult as a Therapy for Neurodegenerative Diseases

2020 ◽  
Vol 21 (3) ◽  
pp. 1021 ◽  
Author(s):  
Carlota Suárez-Barrio ◽  
Susana del Olmo-Aguado ◽  
Eva García-Pérez ◽  
María de la Fuente ◽  
Francisco Muruzabal ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Human Cell Line ◽  
Antioxidant Effect ◽  
Age Related Macular Degeneration ◽  
Strong Impact ◽  
Retinal Diseases ◽  
Age Related ◽  
Gene And Protein Expression

Oxidative stress has a strong impact on the development of retinal diseases such as age-related macular degeneration (AMD). Plasma rich in growth factors (PRGF) is a novel therapeutic approach in ophthalmological pathologies. The aim of this study was to analyze the antioxidant effect of PRGF in retinal epithelial cells (EPR) in in vitro and ex vivo retinal phototoxicity models. In vitro analyses were performed on ARPE19 human cell line. Viability and mitochondrial status were assessed in order to test the primary effects of PRGF. GSH level, and protein and gene expression of the main antioxidant pathway (Keap1, Nrf2, GCL, HO-1, and NQO1) were also studied. Ex vivo analyses were performed on rat RPE, and HO-1 and Nrf2 gene and protein expression were evaluated. The results show that PRGF reduces light insult by stimulating the cell response against oxidative damage and modulates the antioxidant pathway. We conclude that PRGF’s protective effect could prove useful as a new therapy for treating neurodegenerative disorders such as AMD.

scholarly journals Neuroprotective Potential of Ginkgo biloba in Retinal Diseases

Planta Medica ◽  
2019 ◽  
Vol 85 (17) ◽  
pp. 1292-1303 ◽  
Author(s):  
Isabel Martínez-Solís ◽  
Nuria Acero ◽  
Francisco Bosch-Morell ◽  
Encarna Castillo ◽  
María Eugenia González-Rosende ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ginkgo Biloba ◽  
Redox Homeostasis ◽  
Antioxidant Properties ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Age Related ◽  
The Central Nervous System ◽  
Degenerative Processes

AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.

scholarly journals Thermostable small-molecule inhibitor of angiogenesis and vascular permeability that suppresses a pERK-FosB/ΔFosB–VCAM-1 axis

2020 ◽  
Vol 6 (31) ◽  
pp. eaaz7815
Author(s):  
Yue Li ◽  
Ahmad M. N. Alhendi ◽  
Mei-Chun Yeh ◽  
Mina Elahy ◽  
Fernando S. Santiago ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Small Molecule ◽  
Wound Repair ◽  
Network Formation ◽  
Small Molecule Inhibitor ◽  
Age Related Macular Degeneration ◽  
Endothelial Cell Proliferation ◽  
Age Related ◽  
Molecule Inhibitor

Vascular permeability and angiogenesis underpin neovascular age-related macular degeneration and diabetic retinopathy. While anti-VEGF therapies are widely used clinically, many patients do not respond optimally, or at all, and small-molecule therapies are lacking. Here, we identified a dibenzoxazepinone BT2 that inhibits endothelial cell proliferation, migration, wound repair in vitro, network formation, and angiogenesis in mice bearing Matrigel plugs. BT2 interacts with MEK1 and inhibits ERK phosphorylation and the expression of FosB/ΔFosB, VCAM-1, and many genes involved in proliferation, migration, angiogenesis, and inflammation. BT2 reduced retinal vascular leakage following rat choroidal laser trauma and rabbit intravitreal VEGF-A165 administration. BT2 suppressed retinal CD31, pERK, VCAM-1, and VEGF-A165 expression. BT2 reduced retinal leakage in rats at least as effectively as aflibercept, a first-line therapy for nAMD/DR. BT2 withstands boiling or autoclaving and several months’ storage at 22°C. BT2 is a new small-molecule inhibitor of vascular permeability and angiogenesis.

scholarly journals Development of a Deep-Learning-Based Artificial Intelligence Tool for Differential Diagnosis between Dry and Neovascular Age-Related Macular Degeneration

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 261
Author(s):  
Tae-Young Heo ◽  
Kyoung Min Kim ◽  
Hyun Kyu Min ◽  
Sun Mi Gu ◽  
Jae Hyun Kim ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Differential Diagnosis ◽  
Deep Learning ◽  
Macular Degeneration ◽  
Data Augmentation ◽  
Treatment Strategies ◽  
Image Data ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Leave One Out

The use of deep-learning-based artificial intelligence (AI) is emerging in ophthalmology, with AI-mediated differential diagnosis of neovascular age-related macular degeneration (AMD) and dry AMD a promising methodology for precise treatment strategies and prognosis. Here, we developed deep learning algorithms and predicted diseases using 399 images of fundus. Based on feature extraction and classification with fully connected layers, we applied the Visual Geometry Group with 16 layers (VGG16) model of convolutional neural networks to classify new images. Image-data augmentation in our model was performed using Keras ImageDataGenerator, and the leave-one-out procedure was used for model cross-validation. The prediction and validation results obtained using the AI AMD diagnosis model showed relevant performance and suitability as well as better diagnostic accuracy than manual review by first-year residents. These results suggest the efficacy of this tool for early differential diagnosis of AMD in situations involving shortages of ophthalmology specialists and other medical devices.

scholarly journals Fibrovascular pigment epithelial detachment in eyes with subretinal hemorrhage secondary to neovascular AMD or PCV: a morphologic predictor associated with poor treatment outcomes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jae Hui Kim ◽  
Joo Yeon Kim ◽  
Dong Won Lee ◽  
Chul Gu Kim ◽  
Jong Woo Kim
Keyword(s):  
Treatment Outcomes ◽  
Treatment Strategies ◽  
Age Related Macular Degeneration ◽  
Subretinal Hemorrhage ◽  
Pigment Epithelial Detachment ◽  
Neovascular Amd ◽  
Pigment Epithelial ◽  
Age Related ◽  
Poor Treatment ◽  
The Mean

Abstract To evaluate the influence of fibrovascular pigment epithelial detachment (FVPED) on treatment outcomes in eyes with subretinal hemorrhage secondary to neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). This retrospective study included 83 eyes diagnosed with fovea-involving submacular hemorrhage secondary to neovascular AMD or PCV. All the patients were treated with intravitreal anti-vascular endothelial growth factor. Eyes showing definite FVPED, which involves the subfoveal region, were included in the FVPED group. Eyes without subfoveal PED, shallow irregular PEDs, or serous/hemorrhagic PED were stratified to the non-FVPED group. The best-corrected visual acuity (BCVA) at diagnosis, at 3 months, at 12 months, and lesion re-activation after initial treatment were compared between the two groups. The mean size of hemorrhage was 8.6 ± 7.6 disc diameter areas. In the FVPED group, the mean logarithm of minimal angle of resolution BCVA was 1.11 ± 0.49 at diagnosis, 0.89 ± 0.58 at 3 months, and 1.05 ± 0.63 at 12 months. In the non-FVPED group, the values were 0.97 ± 0.56, 0.56 ± 0.55, and 0.45 ± 0.50, respectively. The BCVA at 3 months (P = 0.036) and at 12 months (P < 0.001) was significantly worse in the FVPED group than in the non-FVPED group. In addition, the incidence of lesion reactivation was greater in the FVPED group (83.3%) than in the non-FVPED group (38.5%) (P < 0.001). The presence of subfoveal FVPED was associated with a high incidence of lesion re-activation and poor treatment outcomes in eyes with subretinal hemorrhage. This result suggests that different treatment strategies are needed between eyes with and without FVPED.

scholarly journals Pattern of blindness in a community based hospital of Nepal

2013 ◽  
Vol 5 (1) ◽  
pp. 50-56
Author(s):  
R Sharma ◽  
S Marasini ◽  
BP Nepal
Keyword(s):  
Age Related Macular Degeneration ◽  
Easy Access ◽  
Retinal Diseases ◽  
Access To Health Services ◽  
Community Based ◽  
Cross Sectional ◽  
Age Related ◽  
Access To Health ◽  
Disease Pattern ◽  
The Mean

Introduction: Because of the availability of modern health facilities and moderately easy access to health services in the last 25 years, the blindness due to cataract and trachoma is expected to decline in Nepal. So it is felt that the causes of blindness need to be revised. Objective: To regroup the disease pattern leading to permanent blindness in patients attending a suburban multidisciplinary community-based hospital of Nepal. Materials and methods: A cross-sectional, descriptive study was conducted in patients attending Dhulikhel hospital over a period of 12 months, from March 2010. Only the patients with best corrected visual acuity of < 3/60 were enrolled in the study. A detailed ocular examination was carried out. Results: A total of 76 eyes of 58 patients were analyzed. Of all, 32 were male (55.2 %). The mean age of the patients was 43.03 ± 22.98, with a range of 7 years to 84 years. Retinal diseases had the higher prevalence (23, 39.7 %) followed by amblyopia (10, 17.2 %) and corneal diseases (9, 15.51 %). Anisometropic amblyopia (3.94 %) was the commonest type of amblyopia. Retinitis pigmentosa (9.21 %) and age-related macular degeneration (7.89 %) were common retinal diseases whereas anterior staphyloma (5.26 %) and leucoma (3.94 %) were common corneal diseases. Other important and rare causes of blindness included ethambutol-induced optic neuropathy and vitelliform dystrophy. Conclusion: Periodic collection of statistics on the relative frequency of the causes of blindness is important in socioeconomically developing nations like Nepal. This helps to revise the pattern of blinding diseases so that priorities can be redefined. Nepal J Ophthalmol 2013; 5(9):50-56 DOI: http://dx.doi.org/10.3126/nepjoph.v5i1.7822

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