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1.
Chem Biol Interact ; 394: 110996, 2024 May 01.
Article En | MEDLINE | ID: mdl-38593908

Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18). Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.


Cholesterol , Diabetes Mellitus, Experimental , Diabetic Retinopathy , Gliosis , Light , Rats, Wistar , Retina , Streptozocin , Animals , Male , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Retina/metabolism , Retina/pathology , Retina/radiation effects , Cholesterol/metabolism , Rats , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/complications , Gliosis/pathology , Gliosis/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/genetics , Anti-Inflammatory Agents/pharmacology , Aquaporin 4/metabolism , Aquaporin 4/genetics , Retinal Vessels/metabolism , Retinal Vessels/pathology
3.
Vis Neurosci ; 39: E005, 2022 09 27.
Article En | MEDLINE | ID: mdl-36164752

To study the macroglia and microglia and the immune role in long-time light exposure in rat eyes, we performed glial cell characterization along the time-course of retinal degeneration induced by chronic exposure to low-intensity light. Animals were exposed to light for periods of 2, 4, 6, or 8 days, and the retinal glial response was evaluated by immunohistochemistry, western blot and real-time reverse transcription polymerase chain reaction. Retinal cells presented an increased expression of the macroglia marker GFAP, as well as increased mRNA levels of microglia markers Iba1 and CD68 after 6 days. Also, at this time-point, we found a higher number of Iba1-positive cells in the outer nuclear layer area; moreover, these cells showed the characteristic activated-microglia morphology. The expression levels of immune mediators TNF, IL-6, and chemokines CX3CR1 and CCL2 were also significantly increased after 6 days. All the events of glial activation occurred after 5-6 days of constant light exposure, when the number of photoreceptor cells has already decreased significantly. Herein, we demonstrated that glial and immune activation are secondary to neurodegeneration; in this scenario, our results suggest that photoreceptor death is an early event that occurs independently of glial-derived immune responses.


Interleukin-6 , Neuroglia , Radiation Injuries , Retina , Retinal Degeneration , Animals , Chemokines/genetics , Chemokines/metabolism , Interleukin-6/metabolism , Light , Neuroglia/immunology , RNA, Messenger/genetics , Radiation Injuries/etiology , Radiation Injuries/immunology , Rats , Retina/immunology , Retina/radiation effects , Retinal Degeneration/etiology , Retinal Degeneration/immunology
4.
BMC Complement Med Ther ; 22(1): 224, 2022 Aug 26.
Article En | MEDLINE | ID: mdl-36028853

BACKGROUND: Oxidative stress can induce age-related diseases. Age-related retinal diseases, such as age-related macular degeneration (AMD), are difficult to cure owing to their complicated mechanisms. Although anti-neovascular therapeutics are used to treat wet AMD, vision cannot always be completely restored, and disease progression cannot always be inhibited. Therefore, determining a method to prevent or slow retinal damage is important. This study aimed to investigate the protective effect of a chrysanthemum water extract rich in flavone on the oxidatively stressed retina of mice. METHODS: Light damage was induced to establish oxidative stress mouse models. For in vitro experiments, ARPE-19 cells were cultured and divided into four groups: control, light-damaged, and low- and high-dose chrysanthemum extract. No treatment was administered in the control group. The light-damaged and low- and high-dose chrysanthemum extract groups were exposed to a similar white light level. The chrysanthemum extract was added at a low dose of 0.4 mg/mL or a high dose of 1.0 mg/mL before cell exposure to 2500-lx white light. Reactive oxygen species (ROS) level and cellular viability were measured using MTT and immunofluorescence staining. For in vivo experiments, C57BL/6 J mice were divided into the same four groups. Low- (0.23 g/kg/day) and high-dose (0.38 g/kg/day) chrysanthemum extracts were continuously intragastrically administered for 8 weeks before mouse exposure to 10,000-lx white light. Retinal function was evaluated using electroretinography. In vivo optical coherence tomography and in vitro haematoxylin and eosin staining were performed to observe the pathological retinal changes in each group after light damage. Fluorescein fundus angiography of the arteriovenous vessel was performed, and the findings were analysed using the AngioTool software. TUNEL immunofluorescence staining was used to assess isolated retinal apoptosis. RESULTS: In vitro, increased ROS production and decreased ARPE-19 cell viability were found in the light-damaged group. Improved ARPE-19 cell viability and reduced ROS levels were observed in the chrysanthemum extract treatment groups. In vivo, dysfunctional retinas and abnormal retinal structures were found in the light-damaged group, as well as increased apoptosis in the retinal ganglion cells (RGCs) and inner and outer nuclear layers. The apoptosis rate in the same layers was lower in the chrysanthemum extract treatment groups than in the light-damaged group. The production of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), increased in the treatment groups. NF-κB in the nucleus and TNF-α were more highly expressed in the light-damaged group than in the low- and high-dose chrysanthemum extract groups. CONCLUSIONS: Light damage-induced retinal oxidative stress can lead to ROS accumulation in the retinal tissues. Herein, RGC and photoreceptor layer apoptosis was triggered, and NF-κB in the nucleus and TNF-α were highly expressed in the light-damaged group. Preventive chrysanthemum extract administration decreased ROS production by increasing SOD, CAT, and GSH-Px activities and reversing the negative changes, demonstrating a potential protective effect on the retina.


Chrysanthemum , Light , Plant Extracts , Retina , Animals , Antioxidants , Chrysanthemum/chemistry , Light/adverse effects , Mice , Mice, Inbred C57BL , NF-kappa B , Plant Extracts/pharmacology , Reactive Oxygen Species , Retina/drug effects , Retina/radiation effects , Superoxide Dismutase , Tumor Necrosis Factor-alpha
5.
Nature ; 606(7913): 351-357, 2022 06.
Article En | MEDLINE | ID: mdl-35545677

Death is defined as the irreversible cessation of circulatory, respiratory or brain activity. Many peripheral human organs can be transplanted from deceased donors using protocols to optimize viability. However, tissues from the central nervous system rapidly lose viability after circulation ceases1,2, impeding their potential for transplantation. The time course and mechanisms causing neuronal death and the potential for revival remain poorly defined. Here, using the retina as a model of the central nervous system, we systemically examine the kinetics of death and neuronal revival. We demonstrate the swift decline of neuronal signalling and identify conditions for reviving synchronous in vivo-like trans-synaptic transmission in postmortem mouse and human retina. We measure light-evoked responses in human macular photoreceptors in eyes removed up to 5 h after death and identify modifiable factors that drive reversible and irreversible loss of light signalling after death. Finally, we quantify the rate-limiting deactivation reaction of phototransduction, a model G protein signalling cascade, in peripheral and macular human and macaque retina. Our approach will have broad applications and impact by enabling transformative studies in the human central nervous system, raising questions about the irreversibility of neuronal cell death, and providing new avenues for visual rehabilitation.


Light Signal Transduction , Neurological Rehabilitation , Postmortem Changes , Retina , Animals , Autopsy , Cell Death/radiation effects , Central Nervous System/radiation effects , Humans , Light Signal Transduction/radiation effects , Macaca , Mice , Retina/metabolism , Retina/radiation effects , Time Factors
6.
Cell Mol Life Sci ; 79(3): 152, 2022 Feb 25.
Article En | MEDLINE | ID: mdl-35212809

ATP and adenosine have emerged as important signaling molecules involved in vascular remodeling, retinal functioning and neurovascular coupling in the mammalian eye. However, little is known about the regulatory mechanisms of purinergic signaling in the eye. Here, we used three-dimensional multiplexed imaging, in situ enzyme histochemistry, flow cytometric analysis, and single cell transcriptomics to characterize the whole pattern of purine metabolism in mouse and human eyes. This study identified ecto-nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39), NTPDase2, and ecto-5'-nucleotidase/CD73 as major ocular ecto-nucleotidases, which are selectively expressed in the photoreceptor layer (CD73), optic nerve head, retinal vasculature and microglia (CD39), as well as in neuronal processes and cornea (CD39, NTPDase2). Specifically, microglial cells can create a spatially arranged network in the retinal parenchyma by extending and retracting their branched CD39high/CD73low processes and forming local "purinergic junctions" with CD39low/CD73- neuronal cell bodies and CD39high/CD73- retinal blood vessels. The relevance of the CD73-adenosine pathway was confirmed by flash electroretinography showing that pharmacological inhibition of adenosine production by injection of highly selective CD73 inhibitor PSB-12489 in the vitreous cavity of dark-adapted mouse eyes rendered the animals hypersensitive to prolonged bright light, manifested as decreased a-wave and b-wave amplitudes. The impaired electrical responses of retinal cells in PSB-12489-treated mice were not accompanied by decrease in total thickness of the retina or death of photoreceptors and retinal ganglion cells. Our study thus defines ocular adenosine metabolism as a complex and spatially integrated network and further characterizes the critical role of CD73 in maintaining the functional activity of retinal cells.


5'-Nucleotidase/metabolism , Adenosine/metabolism , Light , Retina/radiation effects , 5'-Nucleotidase/antagonists & inhibitors , 5'-Nucleotidase/genetics , Adenosine Diphosphate/analogs & derivatives , Adenosine Diphosphate/pharmacology , Adenosine Triphosphate/metabolism , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Apoptosis/drug effects , Apoptosis/radiation effects , Apyrase/genetics , Apyrase/metabolism , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Microglia/metabolism , Photoreceptor Cells/metabolism , Retina/metabolism , Retina/physiology , Retinal Ganglion Cells/cytology , Retinal Ganglion Cells/metabolism
8.
Nat Prod Res ; 36(12): 3022-3030, 2022 Jun.
Article En | MEDLINE | ID: mdl-34176391

A new phenylethanoid, hebitol IV (1), along with fifteen known glycosides (2-16), were isolated from water extract of the flower buds of Buddleja officinalis. Their structures were elucidated on the basis of 1 D-NMR, 2 D-NMR and MS data. Molecular docking showed the potential activities of the natural products against VEGFR-2. Bioassay results revealed that the compounds 10 and 14 exhibited strong inhibitory activity against VEGFR-2 with IC50 values of 0.51 and 0.32 µM, respectively. Moreover, the potential retinal protective effects of 10 and 14 were then investigated in the mouse model featuring bright light-induced retinal degeneration. The results demonstrated remarkable photoreceptor protective activities of 10 and 14 in vivo.


Buddleja , Glycosides , Photoreceptor Cells , Retina , Animals , Buddleja/chemistry , Glycosides/chemistry , Glycosides/pharmacology , Mice , Molecular Docking Simulation , Photoreceptor Cells/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Retina/cytology , Retina/drug effects , Retina/radiation effects , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
9.
Med Sci Monit ; 27: e935000, 2021 Dec 24.
Article En | MEDLINE | ID: mdl-34949755

BACKGROUND Over-exposure to visible white light can cause retinal damage. Lotus seedpod proanthocyanidins (LSPCs) possess a variety of biological activities, including potent antioxidant and protective effects. Herein, this study observed whether LSPCs can protect against light exposure-induced retinal damage. MATERIAL AND METHODS We randomly separated 40 Prague-Dawley rats into a control group, a light exposure-induced retinal injury model group, and low-dose (50 mg/kg), medium-dose (100 mg/kg), and high-dose (100 mg/kg) LSPCs groups. Light-induced retinal damage models were established by 5000±200 Lx light treatment for 6 h. Five days and 0.5 h before the light treatment, rats in the LSPCs groups were separately administered 50, 100, and 200 mg/kg LSPCs by gavage. After 7 days, H&E staining of retinal sections was performed and the thickness of the ONL was measured. Oxidative stress-related markers and antioxidant enzymes were measured in serum by biochemical testing. TUNEL staining of retinal sections was also performed. Apoptosis-relevant proteins were examined by RT-qPCR and western blotting. GFAP expression was examined with immunohistochemistry. RESULTS Our H&E staining showed that LSPCs can prevent retinal degeneration following light exposure. Histological analysis showed a significant reduction in the ONL thickness of light exposure-induced retinal injury rats, but LSPCs substantially improved the ONL thickness. LSPCs markedly ameliorated the light-induced increase in levels of MDA, NO, and NOS, and decrease in activity of GSH-Px and SOD. Moreover, LSPCs treatment alleviated light-induced retinal apoptosis and limited the light-induced increase in GFAP expression. CONCLUSIONS LSPCs effectively attenuated light-induced retinal damage through antioxidative stress, anti-apoptosis, and neuroprotective effects.


Antioxidants/pharmacology , Apoptosis/drug effects , Lotus/chemistry , Neuroprotective Agents/pharmacology , Proanthocyanidins/pharmacology , Retina/drug effects , Animals , Apoptosis/radiation effects , Blotting, Western , Dose-Response Relationship, Radiation , Female , In Situ Nick-End Labeling , Light/adverse effects , Male , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Plant Components, Aerial/chemistry , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Retina/radiation effects
10.
Probl Radiac Med Radiobiol ; 26: 284-296, 2021 Dec.
Article En, Uk | MEDLINE | ID: mdl-34965555

One of the current problems of modern radiobiology is determine the characteristics of the manifestation of radiation-induced effects not only at different dose loads, but also at different stages of development of the organism. In previous reports, we have summarized available evidence that at certain ages there is a comparative acceleration of radiation-induced pathological changes in the eye and brain, and the study and assessment of the risk of possible ophthalmic and neurological pathology in remote periods after contamination of radioactive areas. Data of irradiated in utero individuals are possible on the basis of observation of the state of the visual analyzer in persons who underwent intrauterine irradiation in 1986. Therefore, a parallel study of retinal morphometric parameters, amplitude and latency of components of evoked visual potentials in irradiated in utero individuals was performed. OBJECTIVE: to evaluate the retinal morphometric parameters, amplitude and latency components of the evoked visual potentials in intrauterine irradiated persons. MATERIALS AND METHODS: The results of surveys of 16 people irradiated in utero in the aftermath of the Chornobyl disaster were used; the comparison group were residents of Kyiv of the corresponding age (25 people). Optical coherence tomography was performed on a Cirrus HD-OCT, Macular Cube 512x128 study technique was used. At the same time, the study of visual evoked potentials on the inverted pattern was performed, and occipital leads wereanalyzed. Visual evoked potentials were recorded on a reversible chess pattern (VEP) - an electrophysiological test, which is a visual response to a sharp change in image contrast when presenting a reversible image of a chessboard. RESULTS: In those irradiated in utero at the age of 22-25 years, there was a probable increase in retinal thickness in the fovea, there was a tendency to increase the thickness of the retina in the areas around the fovea. When recording visual evoked potentials on a reversible chess pattern in this group, there was a tendency to decrease the amplitudes of components (N75, P100, N145, P200) in the right and left parieto-occipital areas and asymmetric changes in latency of these components. CONCLUSIONS: Early changes of fovea recorded in OCT and decreasing amplitudes of components of visual evoked potentials on the reversible chess pattern at the age of 22 25 years may indicate a risk of development in patients irradiated in utero, early age-related macular degeneration, as well as increased risk and increased risk structures of the visual analyzer.


Abnormalities, Radiation-Induced/physiopathology , Chernobyl Nuclear Accident , Evoked Potentials, Visual/radiation effects , Prenatal Exposure Delayed Effects/physiopathology , Radiation, Ionizing , Retina/anatomy & histology , Retina/radiation effects , Adult , Brain Diseases/physiopathology , Eye Diseases/physiopathology , Female , Humans , Male , Pregnancy , Ukraine , Young Adult
11.
Cells ; 10(11)2021 11 19.
Article En | MEDLINE | ID: mdl-34831470

(1) Background: Ocular exposure to intense light or long-time exposure to low-intensity short-wavelength lights may cause eye injury. Excessive levels of blue light induce photochemical damage to the retinal pigment and degeneration of photoreceptors of the outer segments. Currently, people spend a lot of time watching LED screens that emit high proportions of blue light. This study aims to assess the effects of light emitted by LED tablet screens on pigmented rat retinas with and without optical filters. (2) Methods: Commercially available tablets were used for exposure experiments on three groups of rats. One was exposed to tablet screens, the other was exposed to the tablet screens with a selective filter and the other was a control group. Structure, gene expression (including life/death, extracellular matrix degradation, growth factors, and oxidative stress related genes), and immunohistochemistry in the retina were compared among groups. (3) Results: There was a reduction of the thickness of the external nuclear layer and changes in the genes involved in cell survival and death, extracellular matrix turnover, growth factors, inflammation, and oxidative stress, leading decrease in cell density and retinal damage in the first group. Modulation of gene changes was observed when the LED light of screens was modified with an optical filter. (4) Conclusions: The use of short-wavelength selective filters on the screens contribute to reduce LED light-induced damage in the rat retina.


Light , Retina/pathology , Retina/radiation effects , ADAMTS Proteins/genetics , ADAMTS Proteins/metabolism , Animals , Brain-Derived Neurotrophic Factor/metabolism , Extracellular Matrix/genetics , Extracellular Matrix/metabolism , Gene Expression Regulation/radiation effects , Male , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Oxidative Stress/genetics , Rats , Receptor, trkB/metabolism , Retina/metabolism , Superoxide Dismutase/metabolism , Tissue Inhibitor of Metalloproteinases/genetics , Tissue Inhibitor of Metalloproteinases/metabolism , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism
12.
Invest Ophthalmol Vis Sci ; 62(12): 20, 2021 09 02.
Article En | MEDLINE | ID: mdl-34546324

Purpose: Wavelength and temporal frequency have been found to influence refractive development. This study investigated whether retinal dopamine (DA) plays a role in these processes. Methods: Guinea pigs were randomly divided into nine groups that received different lighting conditions for 4 weeks, as follows: white, green, or blue light at 0, 0.5, or 20.0 Hz. Refractions and axial lengths were measured using streak retinoscopy and A-scan ultrasound imaging. DA and its metabolites were measured by high-pressure liquid chromatography-electrochemical detection. Results: At 0 Hz, green and blue light produced myopic and hyperopic shifts compared with that of white light. At 0.5 Hz, no significant changes were observed compared with those of green or blue light at 0 Hz, whereas white light at 0.5 Hz induced a myopic shift compared with white light at 0 or 20 Hz. At 20 Hz, green and blue light acted like white light. Among all levels of DA and its metabolites, only vitreous 3, 4-dihydroxyphenylacetic acid (DOPAC) levels and retinal DOPAC/DA ratios were dependent on wavelength, frequency, and their interaction. Specifically, retinal DOPAC/DA ratios were positively correlated with refractions in white and green light conditions. However, blue light (0, 0.5, and 20.0 Hz) produced hyperopic shifts but decreased vitreous DOPAC levels and retinal DOPAC/DA ratios. Conclusions: The retinal DOPAC/DA ratio, indicating the metabolic efficiency of DA, is correlated with ocular growth. It may underlie myopic shifts from light exposure with a long wavelength and low temporal frequency. However, different biochemical pathways may contribute to the hyperopic shifts from short wavelength light.


Dopamine/physiology , Emmetropia/physiology , Hyperopia/metabolism , Myopia/metabolism , Retina/radiation effects , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Axial Length, Eye/metabolism , Chromatography, High Pressure Liquid , Guinea Pigs , Hyperopia/diagnosis , Hyperopia/physiopathology , Light , Myopia/diagnosis , Myopia/physiopathology , Refraction, Ocular/physiology , Retina/metabolism , Retinoscopy , Ultrasonography , Vitreous Body/metabolism
13.
Cutan Ocul Toxicol ; 40(4): 376-386, 2021 Dec.
Article En | MEDLINE | ID: mdl-34493133

PURPOSE: Environmental light pollution due to artificial light may increase the rate and severity of retinal diseases, and plant-based nutritional interventions with antioxidant properties have the potential to reverse this phenomenon. We aimed to investigate the potential effects of allyl isothiocyanate (AITC) against white light-emitting diode (LED)-induced retinal degeneration (RD) in the rats. METHODS: Twenty-eight male rats were allocated as: (i) Control, (ii) LED, (iii) LED + AITC (10 mg/kg BW), (iv) LED + AITC (20 mg/kg BW). Rats were administered with AITC for 28 days, followed by two days of intense environmental LED light (750 Lux) exposure to the eyes. Animals were sacrificed immediately at the end of the study, then the blood and eyeballs were taken for the biochemical, western blotting, and histopathology examinations. RESULTS: AITC lowered the serum and retina malondialdehyde (MDA) levels while significantly (p < 0.05) improving the retinal antioxidant enzyme activities in a dose-dependent manner. AITC improved retinal and outer nuclear layer (ONL) thickness as compared to the LED group (p < 0.05). AITC increased the levels of Bax, caspase-3, HO-1, GAP43, and VEGF, while decreasing IL-1ß, IL-6, NF-κB, Bcl-2, GFAP, Grp78, activating ATF4 and ATF6 as compared to the LED group (p < 0.05). CONCLUSION: In conclusion, four weeks of AITC administration to the rats showed specific protective effects against two days of intense LED light-induced retinal damage; through antiinflammatory, antioxidant, anti-apoptotic, and modulating mitochondrial metabolic pathways.


Isothiocyanates/administration & dosage , Light Pollution/adverse effects , Lighting/adverse effects , Protective Agents/administration & dosage , Retinal Degeneration/drug therapy , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Disease Models, Animal , Humans , Lighting/instrumentation , Male , Mitochondria/drug effects , Mitochondria/pathology , Mitochondria/radiation effects , Oxidative Stress/drug effects , Oxidative Stress/radiation effects , Rats , Retina/cytology , Retina/drug effects , Retina/pathology , Retina/radiation effects , Retinal Degeneration/etiology , Retinal Degeneration/pathology , Semiconductors/adverse effects
14.
Int J Mol Sci ; 22(18)2021 Sep 09.
Article En | MEDLINE | ID: mdl-34575905

BACKGROUND: In adult rats we study the short- and long-term effects of focal blue light-emitting diode (LED)-induced phototoxicity (LIP) on retinal thickness and Iba-1+ activation. METHODS: The left eyes of previously dark-adapted Sprague Dawley (SD) rats were photoexposed to a blue LED (20 s, 200 lux). In vivo longitudinal monitoring of retinal thickness, fundus images, and optical retinal sections was performed from 1 to 30 days (d) after LIP with SD-OCT. Ex vivo, we analysed the population of S-cone and Iba-1+ cells within a predetermined fixed-size circular area (PCA) centred on the lesion. RESULTS: LIP resulted in a circular focal lesion readily identifiable in vivo by fundus examination, which showed within the PCAs a progressive thinning of the outer retinal layer, and a diminution of the S-cone population to 19% by 30 d. In parallel to S-cone loss, activated Iba-1+ cells delineated the lesioned area and acquired an ameboid morphology with peak expression at 3 d after LIP. Iba-1+ cells adopted a more relaxed-branched morphology at 7 d and by 14-30 d their morphology was fully branched. CONCLUSION: LIP caused a progressive reduction of the outer retina with loss of S cones and a parallel dynamic activation of microglial cells in the lesioned area.


Light , Retina/pathology , Retina/radiation effects , Animals , Biomarkers , Disease Models, Animal , Disease Susceptibility , Fluorescent Antibody Technique , Microglia/metabolism , Microglia/pathology , Microglia/radiation effects , Rats , Retina/metabolism , Retinal Cone Photoreceptor Cells/metabolism , Retinal Cone Photoreceptor Cells/pathology , Retinal Cone Photoreceptor Cells/radiation effects , Retinal Degeneration/diagnostic imaging , Retinal Degeneration/etiology , Retinal Degeneration/metabolism , Retinal Degeneration/pathology , Time Factors , Tomography, Optical Coherence
15.
J Photochem Photobiol B ; 224: 112306, 2021 Nov.
Article En | MEDLINE | ID: mdl-34562830

Water-filtered infrared A and visible light (wIRA/VIS), shown to reduce chlamydial infections in vitro and in vivo, might represent an innovative therapeutic approach against trachoma, a neglected tropical disease caused by ocular infection with the bacterium C. trachomatis. In this in vivo study, we assessed the impact of wIRA radiation in combination with VIS (wavelength range 595-1400 nm, intensity 2100 W/m2) on the retina and cornea in a guinea pig animal model of inclusion conjunctivitis. We investigated the effects 19 days after wIRA/VIS irradiation by comparing a single and double wIRA/VIS treatment with a sham control. By immunolabeling and western blot analyses of critical heat- and stress-responsive proteins, we could not detect wIRA/VIS-induced changes in their expression pattern. Also, immunolabeling of specific retinal marker proteins revealed no changes in their expression pattern caused by the treatment. Our preclinical study suggests wIRA/VIS as a promising and safe therapeutic tool to treat ocular chlamydial infections.


Cornea/radiation effects , Eye Proteins/radiation effects , Heat-Shock Proteins/radiation effects , Hot Temperature , Infrared Rays , Light , Retina/radiation effects , Animals , Cornea/metabolism , Eye Proteins/metabolism , Guinea Pigs , Heat-Shock Proteins/metabolism , Retina/metabolism , Trachoma/radiotherapy , Trachoma/veterinary , Water
16.
Adv Sci (Weinh) ; 8(20): e2101754, 2021 10.
Article En | MEDLINE | ID: mdl-34448360

Retinoblastoma is one of the most severe ocular diseases, of which current chemotherapy is limited to the repetitive intravitreal injections of chemotherapeutics. Systemic drug administration is a less invasive route; however, it is also less efficient for ocular drug delivery because of the existence of blood-retinal barrier and systemic side effects. Here, a photoresponsive drug release system is reported, which is self-assembled from photocleavable trigonal small molecules, to achieve light-triggered intraocular drug accumulation. After intravenous injection of drug-loaded nanocarriers, green light can trigger the disassembly of the nanocarriers in retinal blood vessels, which leads to intraocular drug release and accumulation to suppress retinoblastoma growth. This proof-of-concept study would advance the development of light-triggered drug release systems for the intravenous treatment of eye diseases.


Drug Carriers/pharmacology , Drug Liberation/drug effects , Retina/drug effects , Retinoblastoma/drug therapy , Administration, Intravenous , Animals , Aqueous Humor/radiation effects , Blood-Retinal Barrier/drug effects , Disease Models, Animal , Drug Carriers/chemistry , Drug Liberation/radiation effects , Humans , Lenses, Intraocular , Light , Mice , Retina/pathology , Retina/radiation effects , Retinoblastoma/genetics , Retinoblastoma/pathology , Topotecan/chemistry , Topotecan/pharmacology , Vitreous Body/drug effects , Vitreous Body/radiation effects
17.
Exp Eye Res ; 210: 108688, 2021 09.
Article En | MEDLINE | ID: mdl-34237304

Bright light exposure in animals results in the selective degeneration of the outer retina, known as "retinal photic injury" (RPI). The susceptibility to RPI differs among rat strains. WKY rats display susceptibility to RPI with extensive retinal degeneration observed in the sagittal eye specimen, whereas LEW strain rats are resistant to it, showing only slight or no degeneration. In the present study, we first established an ethological screening method using the Morris water maze to discern differential susceptibility among the living rats. WKY and LEW were crossed to produce the first filial generation (F1) offspring. Maze-trained individuals were exposed to bright, white light. The screening test results demonstrated that the susceptibility to light-induced visual impairment in rats is a dominant Mendelian susceptibility trait, as F1 rats were susceptible to visual impairment like WKY rats. Therefore, F1 rats were backcrossed with recessive LEW to produce the first backcross offspring (BC1). Subsequent recurrent backcrossing while selecting for the susceptibility, indicated a segregation ratio of ca. 24% in BC1 and BC2 generations, indicating the involvement of two or more genes in the susceptibility. Further, microsatellite analysis of BC1-to-BC4 individuals using microsatellite markers mapped two susceptibility loci on chromosome segments 5q36 and 19q11-q12, named RPI susceptibility (Rpi)1 and Rpi2, respectively. This study provides an insight into mechanisms underlying differential susceptibility, which could help decipher the mechanism underlying the onset/progression of human age-related macular degeneration.


Light/adverse effects , Radiation Injuries, Experimental/genetics , Retina/radiation effects , Retinal Degeneration/genetics , Vision Disorders/genetics , Animals , Disease Models, Animal , Disease Susceptibility , Female , Male , Microsatellite Repeats , Morris Water Maze Test , Quantitative Trait Loci , Radiation Injuries, Experimental/metabolism , Radiation Injuries, Experimental/physiopathology , Rats , Rats, Inbred Lew , Rats, Inbred WKY , Retinal Degeneration/metabolism , Retinal Degeneration/physiopathology , Vision Disorders/metabolism , Vision Disorders/physiopathology
18.
Sci Rep ; 11(1): 13850, 2021 07 05.
Article En | MEDLINE | ID: mdl-34226638

Uncontrolled diabetes has been associated with progression of diabetic retinopathy (DR) in several studies. Therefore, we aimed to investigate systemic and ophthalmic factors related to worsening of DR even after completion of panretinal photocoagulation (PRP). We retrospectively reviewed DR patients who had completed PRP in at least one eye with a 3-year follow-up. A total of 243 eyes of 243 subjects (mean age 52.6 ± 11.6 years) were enrolled. Among them, 52 patients (21.4%) showed progression of DR after PRP (progression group), and the other 191 (78.6%) patients had stable DR (non-progression group). The progression group had higher proportion of proliferative DR (P = 0.019); lower baseline visual acuity (P < 0.001); and higher platelet count (P = 0.048), hemoglobin (P = 0.044), and hematocrit, (P = 0.042) than the non-progression group. In the multivariate logistic regression analysis for progression of DR, baseline visual acuity (HR: 0.053, P < 0.001) and platelet count (HR: 1.215, P = 0.031) were identified as risk factors for progression. Consequently, we propose that patients with low visual acuity or high platelet count are more likely to have progressive DR despite PRP and require careful observation. Also, the evaluation of hemorheological factors including platelet counts before PRP can be considered useful in predicting the prognosis of DR.


Diabetic Retinopathy/epidemiology , Laser Coagulation/adverse effects , Light Coagulation/adverse effects , Retina/diagnostic imaging , Adult , Choroid/pathology , Choroid/radiation effects , Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/etiology , Diabetic Retinopathy/pathology , Disease Progression , Female , Humans , Male , Middle Aged , Platelet Count , Retina/pathology , Retina/radiation effects , Visual Acuity/physiology , Visual Acuity/radiation effects
19.
Bull Exp Biol Med ; 171(2): 286-291, 2021 May.
Article En | MEDLINE | ID: mdl-34173098

We developed a model of retinal degeneration in rabbits based on exposure to light with a wavelength of 405 nm. This model allows reproducing structural and functional disorders in the central parts of the retina, including primarily degeneration of the outer layers of the retina (retinal pigment epithelium and layer of photoreceptor cells), and is designed to study the mechanisms of formation, progression and effectiveness of new drugs and methods of treatment of degenerative diseases of the retina.


Disease Models, Animal , Rabbits , Retinal Degeneration/pathology , Adaptation, Ocular/radiation effects , Animals , Light , Male , Photoreceptor Cells/pathology , Photoreceptor Cells/radiation effects , Retina/pathology , Retina/radiation effects
20.
Elife ; 102021 06 08.
Article En | MEDLINE | ID: mdl-34100720

Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs. We measured the optokinetic response gain of immobilised zebrafish larvae to stimuli of different steradian size and visual field locations. We find that the two eyes are less yoked than previously thought and that spatial frequency tuning is similar across visual field positions. However, zebrafish react most strongly to lateral, nearly equatorial stimuli, consistent with previously reported spatial densities of red, green, and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.


Nystagmus, Optokinetic/physiology , Photic Stimulation/methods , Retina/physiology , Visual Fields/physiology , Animals , Female , Humans , Larva/physiology , Larva/radiation effects , Mice , Mice, Transgenic , Nystagmus, Optokinetic/radiation effects , Retina/radiation effects , Visual Fields/radiation effects , Zebrafish
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