scholarly journals Purinergic–Glycinergic Interaction in Neurodegenerative and Neuroinflammatory Disorders of the Retina

2021 ◽  
Vol 22 (12) ◽  
pp. 6209
Author(s):  
Laszlo G. Harsing ◽  
Gábor Szénási ◽  
Tibor Zelles ◽  
László Köles
Keyword(s):  
Human Vision ◽  
Age Related Macular Degeneration ◽  
Key Factors ◽  
Glycine Release ◽  
Reverse Mode ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
Age Related ◽  
Energy Deprivation ◽  
Potential Interactions

Neurodegenerative–neuroinflammatory disorders of the retina seriously hamper human vision. In searching for key factors that contribute to the development of these pathologies, we considered potential interactions among purinergic neuromodulation, glycinergic neurotransmission, and microglia activity in the retina. Energy deprivation at cellular levels is mainly due to impaired blood circulation leading to increased release of ATP and adenosine as well as glutamate and glycine. Interactions between these modulators and neurotransmitters are manifold. First, P2Y purinoceptor agonists facilitate reuptake of glycine by glycine transporter 1, while its inhibitors reduce reverse-mode operation; these events may lower extracellular glycine levels. The consequential changes in extracellular glycine concentration can lead to parallel changes in the activity of NR1/NR2B type NMDA receptors of which glycine is a mandatory agonist, and thereby may reduce neurodegenerative events in the retina. Second, P2Y purinoceptor agonists and glycine transporter 1 inhibitors may indirectly inhibit microglia activity by decreasing neuronal or glial glycine release in energy-compromised retina. These inhibitions may have a role in microglia activation, which is present during development and progression of neurodegenerative disorders such as glaucomatous and diabetic retinopathies and age-related macular degeneration or loss of retinal neurons caused by thromboembolic events. We have hypothesized that glycine transporter 1 inhibitors and P2Y purinoceptor agonists may have therapeutic importance in neurodegenerative–neuroinflammatory disorders of the retina by decreasing NR1/NR2B NMDA receptor activity and production and release of a series of proinflammatory cytokines from microglial cells.

Characterization of glycine release mediated by glycine transporter 1 stably expressed in HEK-293 cells

1997 ◽  
Vol 49 (1-2) ◽  
pp. 89-94 ◽  
Author(s):  
Kazuko Sakata ◽  
Kohji Sato ◽  
Patrick Schloss ◽  
Heinrich Betz ◽  
Shoichi Shimada ◽  
...  
Keyword(s):  
Hek 293 ◽  
Hek 293 Cells ◽  
Glycine Release ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
293 Cells

Some Operational Characteristics of Glycine Release in Rat Retina: The Role of Reverse Mode Operation of Glycine Transporter Type-1 (GlyT-1) in Ischemic Conditions

2015 ◽  
Vol 41 (1-2) ◽  
pp. 73-85 ◽  
Author(s):  
Adrienn Hanuska ◽  
Gábor Szénási ◽  
Mihaly Albert ◽  
Laszlo Koles ◽  
Agoston Varga ◽  
...  
Keyword(s):  
Rat Retina ◽  
Mode Operation ◽  
Glycine Release ◽  
Reverse Mode ◽  
Glycine Transporter ◽  
Operational Characteristics

scholarly journals Differential effect of dietary antioxidant classes (carotenoids, polyphenols, vitamins C and E) on lutein absorption

2007 ◽  
Vol 97 (3) ◽  
pp. 440-446 ◽  
Author(s):  
Emmanuelle Reboul ◽  
Sinay Thap ◽  
Franck Tourniaire ◽  
Marc André ◽  
Christine Juhel ◽  
...  
Keyword(s):  
Age Related Macular Degeneration ◽  
Human Retina ◽  
Dietary Antioxidants ◽  
Healthy Men ◽  
Age Related ◽  
Dietary Antioxidant ◽  
Potential Interactions ◽  
Full Factorial ◽  
And Oxidative Stress ◽  
Β Carotene

Lutein is assumed to protect the human retina from blue light and oxidative stress and diminish the incidence of age-related macular degeneration. This antioxidant is commonly ingested with other dietary antioxidants. The aim of the present study was to assess whether the main dietary antioxidants, i.e. carotenoids, polyphenols and vitamins C and E, affect lutein absorption. We measured the effect of adding a mixture of antioxidants (500 mg vitamin C, 67 mg (100 IU) vitamin E and 1 g polyphenols) to a lutein-containing meal (18 mg) on the postprandial lutein response in the chylomicron-rich fraction in eight healthy men. Lutein response was weakest ( − 23 %;P = 0·07) after ingestion of the meal containing antioxidants (21·9 (sem4·6)v.28·4 (sem7·2) nmol × h/l). To assess the effect of each class of antioxidants and potential interactions, we subsequently evaluated the effect of various combinations of antioxidants on lutein uptake by human intestinal Caco-2 TC-7 cells. A full factorial design showed that both a mixture of polyphenols (gallic acid, caffeic acid, (+)-catechin and naringenin) and a mixture of carotenoids (lycopene plus β-carotene) significantly (P < 0·05) impaired lutein uptake by ( − 10 to − 30 %), while vitamins C and E had no significant effect. Subsequent experiments showed that the aglycone flavanone naringenin was the only polyphenol responsible for the effect of the polyphenol mixture, and that the carotenoid effect was not carotenoid species-dependent. Taken together, the present results suggest that lutein absorption is not markedly affected by physiological concentrations of vitamins C and E but can be impaired by carotenoids and naringenin.

scholarly journals Oestrogen, ocular function and low-level vision: a review

2014 ◽  
Vol 223 (2) ◽  
pp. R9-R18 ◽  
Author(s):  
Claire V Hutchinson ◽  
James A Walker ◽  
Colin Davidson
Keyword(s):  
Steroid Hormone ◽  
Human Vision ◽  
Age Related Macular Degeneration ◽  
Pharmacological Treatments ◽  
Vascular Effects ◽  
Sex Steroid Hormone ◽  
Low Level ◽  
Beneficial Effects ◽  
The Past ◽  
Age Related

Over the past 10 years, a literature has emerged concerning the sex steroid hormone oestrogen and its role in human vision. Herein, we review evidence that oestrogen (oestradiol) levels may significantly affect ocular function and low-level vision, particularly in older females. In doing so, we have examined a number of vision-related disorders including dry eye, cataract, increased intraocular pressure, glaucoma, age-related macular degeneration and Leber's hereditary optic neuropathy. In each case, we have found oestrogen, or lack thereof, to have a role. We have also included discussion of how oestrogen-related pharmacological treatments for menopause and breast cancer can impact the pathology of the eye and a number of psychophysical aspects of vision. Finally, we have reviewed oestrogen's pharmacology and suggest potential mechanisms underlying its beneficial effects, with particular emphasis on anti-apoptotic and vascular effects.

scholarly journals Xanthophylls Modulate Palmitoylation of Mammalian β-Carotene Oxygenase 2

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 413
Author(s):  
Sheetal Uppal ◽  
Sergey A. Dergunov ◽  
Weiyu Zhang ◽  
Susan Gentleman ◽  
T. Michael Redmond ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Protein Translocation ◽  
Antioxidant Response ◽  
Human Vision ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Extensive Body ◽  
Β Carotene

An extensive body of work has documented the antioxidant role of xanthophylls (lutein and zeaxanthin) in human health and specifically how they provide photoprotection in human vision. More recently, evidence is emerging for the transcriptional regulation of antioxidant response by lutein/lutein cleavage products, similar to the role of β-carotene cleavage products in the modulation of retinoic acid receptors. Supplementation with xanthophylls also provides additional benefits for the prevention of age-related macular degeneration (AMD) and attenuation of Alzheimer’s disease symptoms. Mammalian β-carotene oxygenase 2 (BCO2) asymmetrically cleaves xanthophylls as well as β-carotene in vitro. We recently demonstrated that mouse BCO2 (mBCO2) is a functionally palmitoylated enzyme and that it loses palmitoylation when cells are treated with β-carotene. The mouse enzyme is the easiest model to study mammalian BCO2 because it has only one isoform, unlike human BCO2 with several major isoforms with various properties. Here, we used the same acyl-RAC methodology and confocal microscopy to elucidate palmitoylation and localization status of mBCO2 in the presence of xanthophylls. We created large unilamellar vesicle-based nanocarriers for the successful delivery of xanthophylls into cells. We demonstrate here that, upon treatment with low micromolar concentration of lutein (0.15 µM), mBCO2 is depalmitoylated and shows partial nuclear localization (38.00 ± 0.04%), while treatment with zeaxanthin (0.45 µM) and violaxanthin (0.6 µM) induces depalmitoylation and protein translocation from mitochondria to a lesser degree (20.00 ± 0.01% and 35.00 ± 0.02%, respectively). Such a difference in the behavior of mBCO2 toward various xanthophylls and its translocation into the nucleus in the presence of various xanthophylls suggests a possible mechanism for transport of lutein/lutein cleavage products to the nucleus to affect transcriptional regulation.

scholarly journals Joint Effect of CFH and ARMS2/HTRA1 Polymorphisms on Neovascular Age-Related Macular Degeneration in Chinese Population

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Kai Fang ◽  
Pei Gao ◽  
Jun Tian ◽  
Xueying Qin ◽  
Wenzhen Yu ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Chinese Population ◽  
Cross Validation ◽  
Joint Effect ◽  
Age Related Macular Degeneration ◽  
Gene Variants ◽  
Neovascular Amd ◽  
Common Pathway ◽  
Age Related ◽  
Potential Interactions

Purpose. The etiology of neovascular age-related macular degeneration (nAMD) cannot be completely explained by identified environmental risk factors or single-locus gene variants. This study was to explore the potential interactions among gene variants on nAMD in Chinese population.Methods. 43 SNPs located in different genes were genotyped in 932 Chinese individuals (464 nAMD patients and 468 controls). We explored the potential interactions among gene variants using generalized multifactor dimensionality reduction (GMDR) algorithm and the method to measure the departure from the additivity model.Results. The joint effect that involvedCFHrs1061170 andHTRA1rs3793917 was shown statistically significant (P< 0.001) with the highest cross-validation consistency (10/10) and the best testing balanced accuracy (64.50%). In addition, based on the method to measure the departure from the additivity model, the synergy index (S) was 2.63 (1.09–6.38) and the attributable proportion due to interaction (AP) was 55.7% (21.4%–89.9%), which suggested that a common pathway may exist for these genes for nAMD. Those who carried CC for rs3793917 and TC/CC for rs1061170 were at the highest risk of nAMD (OR: 9.76, 95% CI: 4.65–20.51).Conclusions. Evidence that the joint effect that involvedCFHandARMS2/HTRA1may contribute to the risk of neovascular AMD in Chinese population was obtained.

Age related macular degeneration (ARMD) – pathophysiological and clinical features and therapeutic concepts

2001 ◽  
Vol 58 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ursula Körner-Stiefbold
Keyword(s):  
Macular Degeneration ◽  
Clinical Features ◽  
Altersbedingte Makuladegeneration ◽  
Age Related Macular Degeneration ◽  
Genetische Faktoren ◽  
Age Related ◽  
Therapeutic Concepts

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.

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