scholarly journals Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1913
Author(s):  
Rahmeh Othman ◽  
Gael Cagnone ◽  
Jean-Sébastien Joyal ◽  
Elvire Vaucher ◽  
Réjean Couture
Keyword(s):  
Renin Angiotensin System ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Kinin System ◽  
Physiological Processes ◽  
Kinin Receptors ◽  
Age Related ◽  
Kallikrein Kinin System ◽  
Retinal Pathologies ◽  
G Protein Coupled

The kallikrein-kinin system (KKS) contributes to retinal inflammation and neovascularization, notably in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD). Bradykinin type 1 (B1R) and type 2 (B2R) receptors are G-protein-coupled receptors that sense and mediate the effects of kinins. While B2R is constitutively expressed and regulates a plethora of physiological processes, B1R is almost undetectable under physiological conditions and contributes to pathological inflammation. Several KKS components (kininogens, tissue and plasma kallikreins, and kinin receptors) are overexpressed in human and animal models of retinal diseases, and their inhibition, particularly B1R, reduces inflammation and pathological neovascularization. In this review, we provide an overview of the KKS with emphasis on kinin receptors in the healthy retina and their detrimental roles in DR and AMD. We highlight the crosstalk between the KKS and the renin–angiotensin system (RAS), which is known to be detrimental in ocular pathologies. Targeting the KKS, particularly the B1R, is a promising therapy in retinal diseases, and B1R may represent an effector of the detrimental effects of RAS (Ang II-AT1R).

Ocular Carotenoid Status in Health and Disease

2019 ◽  
Vol 39 (1) ◽  
pp. 95-120 ◽  
Author(s):  
Lydia Sauer ◽  
Binxing Li ◽  
Paul S. Bernstein
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Light Damage ◽  
Nutritional Interventions ◽  
Age Related ◽  
Dietary Nutrients ◽  
Health And Disease ◽  
Noninvasive Assessment ◽  
Retinal Pathologies

Retinal carotenoids are dietary nutrients that uniquely protect the eye from light damage and various retinal pathologies. Their antioxidative properties protect the eye from many retinal diseases, such as age-related macular degeneration. As many retinal diseases are accompanied by low carotenoid levels, accurate noninvasive assessment of carotenoid status can help ophthalmologists identify the patients most likely to benefit from carotenoid supplementation. This review focuses on the different methods available to assess carotenoid status and highlights disease-related changes and potential nutritional interventions.

scholarly journals Pathways and disease-causing alterations in visual chromophore production for vertebrate vision

2020 ◽  
pp. jbc.REV120.014405 ◽  
Author(s):  
Philip D Kiser ◽  
Krzysztof Palczewski
Keyword(s):  
Retinal Dystrophy ◽  
Bright Light ◽  
Photoreceptor Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Visual Cycle ◽  
Light Conditions ◽  
Age Related ◽  
G Protein Coupled ◽  
Rod And Cone Photoreceptors

All that we view of the world begins with an ultrafast cis to trans photoisomerization of the retinylidene chromophore associated with the visual pigments of rod and cone photoreceptors. The continual responsiveness of these photoreceptors is then sustained by regeneration processes that convert the trans- retinoid back to an 11-cis configuration. Recent biochemical and electrophysiological analyses of the retinal G protein-coupled receptor (RGR) suggest that it could sustain the responsiveness of photoreceptor cells, particularly cones, even under bright light conditions. Thus, two mechanisms have evolved to accomplish the re-isomerization: one involving the well-studied retinoid isomerase (RPE65), and a second photoisomerase reaction mediated by the RGR. Impairments to the pathways that transform all- trans-retinal back to 11-cis-retinal are associated with mild to severe forms of retinal dystrophy. Moreover, with age there also is a decline in the rate of chromophore regeneration. Both pharmacological and genetic approaches are being used to bypass visual cycle defects and consequently mitigate blinding diseases.  Rapid progress in the use of genome editing also is paving the way for the treatment of disparate retinal diseases. In this review, we provide an update on visual cycle biochemistry and then discuss visual cycle-related diseases and emerging therapeutics for these disorders. There is hope that these advances will be helpful in treating more complex diseases of the eye, including age-related macular degeneration (AMD).

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 Kinins and Kinin Receptors in Cardiovascular and Renal Diseases

2021 ◽  
Vol 14 (3) ◽  
pp. 240
Author(s):  
Jean-Pierre Girolami ◽  
Nadine Bouby ◽  
Christine Richer-Giudicelli ◽  
Francois Alhenc-Gelas
Keyword(s):  
Experimental Studies ◽  
Physiological Role ◽  
Renal Diseases ◽  
Kinin System ◽  
Genetic Studies ◽  
Pharmacological Manipulation ◽  
Kininase Ii ◽  
Kinin Receptors ◽  
Kallikrein Kinin System

This review addresses the physiological role of the kallikrein–kinin system in arteries, heart and kidney and the consequences of kallikrein and kinin actions in diseases affecting these organs, especially ischemic and diabetic diseases. Emphasis is put on pharmacological and genetic studies targeting kallikrein; ACE/kininase II; and the two kinin receptors, B1 (B1R) and B2 (B2R), distinguished through the work of Domenico Regoli and his collaborators. Potential therapeutic interest and limitations of the pharmacological manipulation of B1R or B2R activity in cardiovascular and renal diseases are discussed. This discussion addresses either the activation or inhibition of these receptors, based on recent clinical and experimental studies.

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 Improving Efficiency in Separating Blood Vessels from Retinal Images with Deep Learning Techniques

2019 ◽  
Vol 8 (2S11) ◽  
pp. 3637-3640
Keyword(s):  
Diabetic Retinopathy ◽  
Deep Learning ◽  
Macular Degeneration ◽  
Blood Vessels ◽  
Age Related Macular Degeneration ◽  
Retinal Images ◽  
Retinal Vessels ◽  
Age Related ◽  
Learning Techniques ◽  
Retinal Pathologies

Retinal vessels ID means to isolate the distinctive retinal configuration issues, either wide or restricted from fundus picture foundation, for example, optic circle, macula, and unusual sores. Retinal vessels recognizable proof investigations are drawing in increasingly more consideration today because of pivotal data contained in structure which is helpful for the identification and analysis of an assortment of retinal pathologies included yet not restricted to: Diabetic Retinopathy (DR), glaucoma, hypertension, and Age-related Macular Degeneration (AMD). With the advancement of right around two decades, the inventive methodologies applying PC supported systems for portioning retinal vessels winding up increasingly significant and coming nearer. Various kinds of retinal vessels segmentation strategies discussed by using Deep Learning methods. At that point, the pre-processing activities and the best in class strategies for retinal vessels distinguishing proof are presented.

scholarly journals Ecotin-Like ISP ofL. majorPromastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2and B1Receptors

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Erik Svensjö ◽  
Larissa Nogueira de Almeida ◽  
Lucas Vellasco ◽  
Luiz Juliano ◽  
Julio Scharfstein
Keyword(s):  
G Protein ◽  
Leishmania Major ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Kinin System ◽  
Enzymatic Assays ◽  
Macrophage Phagocytosis ◽  
Plasma Leakage ◽  
Kallikrein Kinin System ◽  
G Protein Coupled

Inhibitors of serine peptidases (ISPs) expressed byLeishmania majorenhance intracellular parasitism in macrophages by targeting neutrophil elastase (NE), a serine protease that couples phagocytosis to the prooxidative TLR4/PKR pathway. Here we investigated the functional interplay between ISP-expressingL. majorand the kallikrein-kinin system (KKS). Enzymatic assays showed that NE inhibitor or recombinant ISP-2 inhibited KKS activation in human plasma activated by dextran sulfate. Intravital microscopy in the hamster cheek pouch showed that topically appliedL. majorpromastigotes (WT andΔisp2/3mutants) potently induced plasma leakage through the activation of bradykinin B2receptors (B2R). Next, using mAbs against kininogen domains, we showed that these BK-precursor proteins are sequestered byL. majorpromastigotes, being expressed at higher % in theΔisp2/3mutant population. Strikingly, analysis of the role of kinin pathway in the phagocytic uptake ofL. majorrevealed that antagonists of B2R or B1R reversed the upregulated uptake ofΔisp2/3mutants without inhibiting macrophage internalization of WTL. major. Collectively, our results suggest thatL. majorISP-2 fine-tunes macrophage phagocytosis by inhibiting the pericellular release of proinflammatory kinins from surface bound kininogens. Ongoing studies should clarify whetherL. majorISP-2 subverts TLR4/PKR-dependent prooxidative responses of macrophages by preventing activation of G-protein coupled B2R/B1R.

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.

Steroid induced changes of the renal kallikrein-kinin system in rats

1984 ◽  
Vol 107 (1) ◽  
pp. 131-140 ◽  
Author(s):  
G. Bönner ◽  
R. Autenrieth ◽  
M. Marin-Grez ◽  
G. Speck ◽  
F. Gross
Keyword(s):  
Urinary Excretion ◽  
Time Course ◽  
Urine Volume ◽  
Renin Angiotensin System ◽  
Sprague Dawley ◽  
Kinin System ◽  
Salt Loading ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System ◽  
Kallikrein Activity

Abstract. In male Sprague-Dawley rats the influence of salt loading (1% NaCl), deoxycorticosterone acetate (2 × 15 mg/kg/day resp. 250 mg/kg sc), corticosterone (2 × 20 mg/kg/day sc) and adrenocorticosterone (0.5 mg/kg/day tetracosactid sc) on the activity of renal kallikrein and renal renin activity was investigated. Salt loading lowered renal kallikrein activity, deoxycorticosterone stimulated its activity and in combination they had no effect on renal kallikrein activity. The time course of kallikrein stimulation by deoxycorticosterone showed no relationship to the escape phenomenon of the kidney from the sodium retaining effect of the mineralocorticoid hormone. Reduction of endogenous mineralcorticoid hormones by adrenalectomy caused a marked reduction of urinary and renal kallikrein activity. Corticosterone suppressed the activity of the renal kallikrein-kinin system at the same time as the reduction in urinary aldosterone excretion. Adrenocorticotrophin caused the same decrease in the activity of renal kallikrein as corticosterone. Urinary aldosterone excretion, however, was significantly stimulated. Thus, the known positive correlation between kallikrein and aldosterone was missing. In all experiments the urinary excretion of kallikrein correlated highly with the kallikrein activity measured in renal cortical tissue. However, no correlation was found between kallikrein and urine volume or urinary excretion of sodium and potassium. In our experiments no relationship between the activity of the renin-angiotensin system and that of the renal kallikrein-kinin system was observed. Furthermore, no clear relationship was found between systemic blood pressure and the activity of the renal kallikrein-kinin system.

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