sodium-iodate and Retinal-Diseases

Topics: Animals; Humans; Iodates; Microscopy, Electron; Pigment Epithelium of Eye; Regeneration; Retinal Diseases

Dry age-related macular degeneration (dAMD) is a chronic degenerative ophthalmopathy that leads to serious burden of visual impairment. Antioxidation in retinal pigment epithelium (RPE) cells is considered as a potential treatment for dAMD. Our previous studies have showed that naringenin (NAR) protects RPE cells from oxidative damage partly through SIRT1-mediated antioxidation. In this study, we tested the hypothesis that the Nrf2 signaling is another protective mechanism of NAR on dAMD. NaIO

Topics: Animals; Estrogen Antagonists; Female; Flavanones; Gene Expression Regulation; Iodates; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Protective Agents; Reactive Oxygen Species; Retinal Diseases; Retinal Pigment Epithelium; Up-Regulation

Glycyrrhizin is a bioactive triterpenoid saponin extracted from a traditional Chinese medicinal herb, glycyrrhiza, and has been reported to protect the organs such as liver and heart from injuries. However, there is no report about the effects of glycyrrhizin on atrophic age-related macular degeneration (AMD). This study investigated the effects of glycyrrhizin on retinal pigment epithelium (RPE) in vitro and retina of mice in vivo treated with sodium iodate (SI). Glycyrrhizin significantly inhibited SI-induced reactive oxygen species (ROS), and decreased apoptosis of RPE in vitro. The underlying mechanisms included increased phosphorylation of Akt, and increased expression of nuclear factor erythroid 2-related factor2 (Nrf-2) and HO-1, thereby protecting RPE from SI-induced ROS and apoptosis. Furthermore, glycyrrhizin significantly decreased the apoptosis of retinal cells in vivo, resulting in the inhibition of thinning of retina, decreasing the number of drusen and improving the function of retina. These findings suggested that glycyrrhizin may be a potential candidate for the treatment of atrophic AMD in clinical practice.

Topics: Animals; Apoptosis; Cell Line; Glycyrrhizic Acid; Heme Oxygenase-1; Humans; Iodates; Male; Mice, Inbred C57BL; NF-E2-Related Factor 2; Protective Agents; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Retina; Retinal Diseases; Retinal Pigment Epithelium; Signal Transduction

Transplantation of stem cells is one of the approaches to treat retinal diseases. Our objective was to determine whether adipose-derived stem cell transplant can survive and migrate in the injured retina using a sodium iodate model for the pigmented retinal epithelium injury.. The adipose-derived stem cells were isolated from male albino Sprague-Dawley rats and labeled with DiI so as to track the transplants in the subretinal space. Retinal pigmented epithelium damage was induced by retro-orbital sinus sodium iodate injection (40 mg/kg) into albino Sprague-Dawley rats. Four weeks after transplantation, the eyeballs were fixed in 4% paraformaldehyde and cut with cryostat. The eyeballs were serially sectioned along the vertical meridian. Cryosections were from the full length of the retina and passing through the optic nerve head. The survival and migration of transplanted cells were assessed.. Sodium iodate selectively destroyed the retinal pigmented epithelium layer. The transplanted cells incorporated into the retinal pigmented epithelium layer, perhaps differentiating into a retinal pigmented epithelium phenotype. The transplanted cells were located in the subretinal space; after 4 weeks, some were observed in the retinal pigmented epithelium layer.. We found that adipose-derived stem cells survived for 4 weeks after transplantation and migrated into the retinal pigmented epithelium layer.

Topics: Adipose Tissue; Animals; Cell Differentiation; Cell Movement; Cell Survival; Cells, Cultured; Disease Models, Animal; Iodates; Male; Phenotype; Rats, Sprague-Dawley; Retinal Diseases; Retinal Pigment Epithelium; Stem Cell Transplantation

Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement of RPE is discussed as a potential therapy for AMD. Previous studies were performed in animal models with severe limitations in recapitulating the disease progression. In detail, we describe the effect of systemic injection of sodium iodate in the mouse retina. We further evaluate the usefulness of this animal model to analyze cell-specific effects following transplantation of human embryonic stem cell (hESC)-derived RPE cells.. Morphologic, functional, and behavioral changes following sodium iodate injection were monitored by histology, gene expression analysis, electroretinography, and optokinetic head tracking. Human embryonic stem cell-derived RPE cells were transplanted 1 week after sodium iodate injection and experimental retinae were analyzed 3 weeks later.. Injection of sodium iodate caused complete RPE cell loss, photoreceptor degeneration, and altered gene and protein expression in outer and inner nuclear layers. Retinal function was severely affected by day 3 and abolished from day 14. Following transplantation, donor hESC-derived RPE cells formed extensive monolayers that displayed wild-type RPE cell morphology, organization, and function, including phagocytosis of host photoreceptor outer segments.. Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nuclear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants. The availability of an RPE-free Bruch's membrane in this model likely allows the unprecedented formation of extensive polarized cell monolayers from donor hESC-derived RPE cell suspensions.

Topics: Animals; Cell Transplantation; Disease Models, Animal; Iodates; Mice, Inbred C57BL; Photoreceptor Cells, Vertebrate; Retinal Diseases; Retinal Pigment Epithelium

The purpose of this study was to appraise the functional response of damaged retina to the stem cell-based therapy in mice. The majority of disorders leading to the irreversible vision loss in the developed world is caused by retinal degeneration. Since, recent reports emphasized regenerative potential of bone marrow stem marrow stem/progenitor cells (SPCs), we investigated here the beneficial effect of intravenously administrated SPCs on regeneration of acutely injured retina.. Selective chemical injury of murine retinas was induced by intravenous administration of sodium iodate (NalO3) in its toxic dose. Flash electroretinogram (ERG), was performed in different time points after infusion of bone marrow-derived and negative for linage antigens population of SPCs.. Stem cell-based therapy resulted in gradual increase of b-wave amplitude in ERG recordings starting from the 3rd day after NalO3 administration, what confirmed the improvement of retinal function in long-term observation.. Our preliminary findings revealed that the selected stem cell-based therapy employed in the adjuvant mode has been shown to be effective in supporting the retinal function recovery after acute retinal damage.

Topics: Animals; Bone Marrow Transplantation; Disease Models, Animal; Electroretinography; Hematopoietic Stem Cell Transplantation; Iodates; Mice; Mice, Inbred C57BL; Regeneration; Retina; Retinal Diseases; Treatment Outcome

To correlate damage to the retinal pigment epithelium (RPE) with decreased visual function after the systemic administration of sodium iodate (NaIO(3)).. Damage was produced in mice by injection of 15, 25, or 35 mg/kg NaIO(3). Visual function was assessed with the cued water maze (WM) behavioral test and the optokinetic reflex (OKR) measurement at different times after injection. Autofluorescence in whole eye flatmounts was quantified, and hematoxylin and eosin staining of paraffin sections was performed to assess changes in the outer retina.. After 15 mg/kg NaIO(3), cued WM test results were normal, whereas OKR measurements were significantly decreased at all times. Focal RPE loss began on day 21, but no significant damage to the outer nuclear layer was observed. After 25 mg/kg NaIO(3), the cued WM test was transitionally reduced and the OKR measurement again decreased at all times. Large areas of RPE loss occurred on day 14 with a reduced outer nuclear layer on the same day. With 35 mg/kg NaIO(3), the cued WM test was reduced beginning on day 14 with complete obliteration of the OKR beginning on day 3, large areas of RPE loss on the same day, and a reduced outer nuclear layer on day 7.. Stable, patchy RPE loss was observed with a low concentration of NaIO(3). The OKR measurement showed changes in visual function earlier than the cued WM test and before histologic findings were observed.

Topics: Animals; Behavior, Animal; Injections, Intravenous; Iodates; Male; Maze Learning; Mice; Mice, Inbred C57BL; Nystagmus, Optokinetic; Psychomotor Performance; Retinal Diseases; Retinal Pigment Epithelium; Vision Disorders; Visual Acuity

Full-field electroretinography (ERG) using contact lenses with built-in LED was performed on albino rats, and used to evaluate the visual toxicity of sodium iodate (NaIO(3)). Experiment 1 was carried out to determine the optimal conditions in rats relating to stimulus intensity, background illumination, and light adaptation period. As a result, we found that a full-field ERG was recorded under the following conditions: stimulus intensity: -3.5 log cd s/m(2) in rod response; background intensity and light adaptation period: 10 cd/m(2) and 10 min in cone and flicker responses. Experiment 2 was carried out to confirm the usefulness of full-field ERG using rats with retinal toxicities induced by NaIO(3). Male rats were given NaIO(3) intravenously at a dose of 50 mg/kg. ERG was recorded before administration and after 3, 8, 24 h, and 7 days of administration, and histopathological analysis was conducted after 8 h of administration. The rod response disappeared completely at 3 h, based on a reduced maximal response and oscillatory potentials. On the other hand, cone and flicker responses were still present at 8 h. All responses disappeared on the 7th day. These findings indicate that the retinal toxicity induced by NaIO(3) was expressed first in rods, followed by cones. There were no microscopical changes after 8 h of administration, although the rod responses had completely disappeared by this time. These results suggest that full-field ERG in rats using an LED contact lens is useful for the separate evaluation of toxic effects on rods and cones.

Topics: Animals; Contact Lenses; Electroretinography; Iodates; Light; Male; Microelectrodes; Photoreceptor Cells, Vertebrate; Rats; Retinal Diseases

To provide proof-of-concept that the extent of intraretinal manganese uptake after systemic MnCl(2) injection, detected with manganese-enhanced MRI (MEMRI), assesses alterations in intraretinal ion demand in models of ocular insult.. In Sprague-Dawley rats, retinal ion demand and thickness were measured from MEMRI data collected before, 4 hours after, or 1, 3, and 7 days after intraperitoneal injection of MnCl(2). Choroidal contribution or blood-retinal barrier permeability surface area product (BRB PS') was determined using MRI after Gd-DTPA injection. Ocular injury was evaluated 24 hours after intravitreal injection of phosphate-buffered saline (PBS, vehicle) or PBS + ouabain, or after intraperitoneal injection of sodium iodate. Manganese retinal toxicity was assessed by comparing full-field, white-flash electroretinographic (ERG) data obtained before and after systemic MnCl(2) administration. Rat choroidal thickness was measured from cross-sections prepared from paraformaldehyde-perfused adult rats.. Comparing pre- and post-Gd-DTPA images demonstrated minimal choroidal contribution to intraretinal analysis. Intraretinal signal intensity returned to baseline by 7 days after MnCl(2) injection. After ouabain injection, receptor and postreceptor uptake of manganese were subnormal (P < 0.05). After sodium iodate exposure, intraretinal manganese uptake was supernormal (P < 0.05) and did not increase with increasing BRB PS'. ERG data did not show any effect of MnCl(2) on photoreceptor a-wave and postreceptor b-wave relative to baseline at either observation time.. MEMRI measurements of uptake of systemically administered and nontoxic doses of manganese appear to be a powerful approach for measuring alteration in intraretinal ion demand in models of ocular injury.

Topics: Animals; Blood-Retinal Barrier; Chlorides; Choroid; Contrast Media; Electroretinography; Enzyme Inhibitors; Female; Gadolinium DTPA; Iodates; Magnetic Resonance Imaging; Manganese Compounds; Models, Biological; Ouabain; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Retina; Retinal Diseases

The time-course of dark adaptation provides valuable insights into the function and interactions between the rod and cone pathways in the retina. Here we describe a technique that uses the flash electroretinogram (ERG) response to probe the functional integrity of the cone and rod pathways during the dynamic process of dark adaptation in the mouse. Retinal sensitivity was estimated from the stimulus intensity required to maintain a 30 microV criterion b-wave response during a 40 min period of dark adaptation. When tracked in this manner, dark adaptation functions in WT mice depended upon the bleaching effects of initial background adaptation conditions. Altered dark adaptation functions, commensurate with the functional deficit were recorded in pigmented mice that lacked cone function (Gnat2 ( cplf3 )) and in WT mice injected with a toxin, sodium iodate (NaIO(3)), which targets the retinal pigment epithelium and also has downstream effects on photoreceptors. These data demonstrate that this adaptive tracking procedure measures retinal sensitivity and the contributions of the rod and/or cone pathways during dark adaptation in both WT control and mutant mice.

Topics: Animals; Dark Adaptation; Electroretinography; Iodates; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Retina; Retinal Cone Photoreceptor Cells; Retinal Diseases; Retinal Rod Photoreceptor Cells; Time Factors

The purpose of this study is to examine the relationship between pathological changes of the choriocapillaris (CC) and the finding of bright fluorescence on indocyanine green (ICG) angiography.. An animal model was used, with chorioretinal lesions produced by injecting sodium iodate 3 h, 24 h, 7 days or 14 days previously. The ICG angiographic findings were compared with histology.. Three hours after injection, many spots of bright fluorescence were scattered at the posterior pole. Histologically, variable changes in CC endothelial cells were observed. In some regions, the cells remained almost normal morphologically. In other regions, the endothelial cytoplasm was thickened with decreased fenestrations, or precipitation of fibrin in the choroidal interstitium was observed. Twenty-four hours after injection, the area of bright fluorescence had extended beyond that observed after 3 h. Histologically, the cytoplasmic structure of CC endothelial cells was unclear, and the endothelial walls were detached from the basement membrane. When ferritin was administered as a tracer, many ferritin granules were observed in Bruch's membrane. Seven days after injection, the degree of bright fluorescence was reduced as compared with 3 and 24 h after injection. Histologically, the cytoplasm of CC endothelial cells was thinned, but contained few fenestrations. The endothelial walls were detached from the basement membrane. Fourteen days after injection, normal diffuse ICG fluorescence was observed. Histologically, CC endothelial cells exhibited almost normal structure.. These findings indicate that changes in CC endothelial cells and bright fluorescence on ICG angiography are closely related. ICG angiography should enable clinical evaluation of increased permeability of CC endothelial cells to relatively large molecules.

Topics: Animals; Capillaries; Capillary Permeability; Choroid; Choroid Diseases; Disease Models, Animal; Endothelium, Vascular; Ferritins; Fluorescein Angiography; Fluorescent Dyes; Indocyanine Green; Iodates; Rabbits; Retinal Diseases

Contrast-enhanced magnetic resonance imaging (MRI) is a promising method for investigating the breakdown of the blood-retinal barrier (BRB). However, subtle intensity changes due to low concentrations of contrast agent can be difficult to detect without observer bias. In this study, we developed a temporal correlation method for detecting these subtle signal intensity changes. The method was evaluated in eyes with chemically induced retinal lesions of known size. A time series of MRI data were collected following i.v. administration of different doses of gadolinium-diethylaminetriaminepentaacetic acid (0.05, 0.1, 0.5 mmol/kg). These time course images were analyzed by temporal correlation to a reference enhancement curve. The reference curve was generated based on a validated theoretical enhancement curve. The temporal correlation method detected signal intensity changes in cases where the changes were too subtle to be visible on a postinjection image or a subtraction image (obtained by subtracting the precontrast image from the final image in the time course set). In addition, assessment of leakage was performed by viewing each image in the set with an eight gray-level palette. Areas of leakage identified in this manner corresponded to those identified by temporal correlation, a finding which supports the validity of the temporal correlation method. These results suggest that temporal correlation may be a time-efficient way to screen large numbers of image data sets using an objective, user-independent criterion.

Topics: Algorithms; Animals; Blood-Retinal Barrier; Contrast Media; Female; Gadolinium; Gadolinium DTPA; Image Enhancement; Iodates; Magnetic Resonance Imaging; Male; Models, Biological; Models, Chemical; Organometallic Compounds; Pentetic Acid; Pigment Epithelium of Eye; Rabbits; Reproducibility of Results; Retinal Diseases; Subtraction Technique; Time Factors; Vitreous Body

The aim of this study was to identify changes in Müller cell plasma membrane specializations during experimentally induced subretinal gliosis in rabbits. When rabbits are dosed with sodium iodate, large expanses of retinal pigment epithelium and photoreceptors are destroyed. They are replaced by a subretinal scar consisting mainly of the ascending processes of Müller cells. These processes transform from the slender, highly polarized structures seen in normal animals into irregular processes that form a glia limitans along the basement membrane of the pigment epithelium, left bare following its degeneration. As the scar processes extend through the subretinal space and contract this basement membrane, they undergo dramatic changes in shape that are especially apparent in three-dimensional computer reconstructions of serial thick sections examined by high-voltage electron microscopy. Other changes involve the intercellular junctions and apical microvilli normally associated with the external limiting membrane. These structures become scattered over the surfaces of the ascending processes and are eventually lost. Loss of microvilli is associated with disappearance of immunostaining for a specific glycoconjugate normally associated with the microvillar plasma membrane. The observations document profound changes in Müller cell structural and functional polarity during subretinal scar formation.

Topics: Animals; Cell Membrane; Female; Intercellular Junctions; Iodates; Microvilli; Pigment Epithelium of Eye; Rabbits; Retina; Retinal Diseases

Dynamic T1-weighted magnetic resonance imaging (MRI) after the injection of Gd-DTPA is a promising method for investigating breakdown of the blood-retinal barrier (BRB). Previously, the authors demonstrated that in a T1-weighted image, the initial rate of change in the vitreous water MRI signal as gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enters the vitreous space strongly correlated with the extent of BRB breakdown. Here, a practical approach to measuring a more relevant physiologic parameter is presented: the permeability surface area product (PS). The theory is a development of earlier work used in investigating the breakdown of the blood-brain barrier. The accuracy and precision of this approach was investigated in rabbits pretreated with sodium iodate (30 mg/kg intravenously). The MRI-derived PS normalized to the area of leaky retina (5.65 +/- 0.25 x 10(-4) cm/min, mean +/- standard error of the mean; n = 6) was compared to a similarly normalized PS calculated using a classical physiologic method (4.12 +/- 0.73 x 10(-4) cm/min; n = 6). Good agreement between the two methods was found (P = 0.09). This result demonstrates that the MRI-derived PS is an accurate and precise measure of BRB breakdown under these conditions. The mathematical model of Gd-DTPA distribution in vivo also is validated. Based on these results, several potential sources of error are discussed, including the effect of back-flow of Gd-DTPA from the vitreous space to the plasma, the underlying vascular patency, and MRI slice selection.

Topics: Animals; Blood-Retinal Barrier; Cell Membrane Permeability; Contrast Media; Female; Gadolinium; Gadolinium DTPA; Iodates; Magnetic Resonance Imaging; Male; Mathematics; Organometallic Compounds; Pentetic Acid; Rabbits; Reproducibility of Results; Retinal Diseases; Vitreous Body

Real-time contrast-enhanced magnetic resonance imaging (MRI) was used to distinguish between experimentally induced breakdown of the vascular (inner) and retinal pigment epithelial (RPE; outer) blood-retinal barrier (BRB) in vivo. Pigmented rabbits were treated with intravenous sodium iodate 30 mg/kg, (a specific RPE cell poison), intravitreal N-ethylcarboxamidoadenosine (NECA) 10(-3) mol/l (which specifically disrupts the vascular BRB), or retinal diode laser photocoagulation. Coronal T1-weighted proton images were acquired in a timed sequence after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Images were analyzed to localize leakage of Gd-DTPA and determine the permeability surface area product normalized per unit area (PS). The pattern of enhancement observed in eyes treated with sodium iodate differed clearly from that in eyes treated with NECA. PS' values were significantly higher in eyes treated with sodium iodate than with NECA. Simultaneous leakage from the outer and inner BRB in eyes treated with dense retinal laser photocoagulation could be localized and quantitated independently.

Topics: Adenosine; Adenosine-5'-(N-ethylcarboxamide); Animals; Blood-Retinal Barrier; Cell Membrane Permeability; Contrast Media; Female; Gadolinium; Gadolinium DTPA; Image Processing, Computer-Assisted; Iodates; Laser Coagulation; Magnetic Resonance Imaging; Male; Organometallic Compounds; Pentetic Acid; Pigment Epithelium of Eye; Rabbits; Retinal Diseases

Topics: Disease; Iodates; Iodides; Iodine; Lipid Metabolism; Lipids; Retina; Retinal Diseases; Sodium