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Retinitis pigmentosa (RP) is a group of inherited retinal disorders that lead to photoreceptor loss. RP has been reported to be related to oxidative stress, autophagy, and inflammation. (-)-Epigallocatechin gallate (EGCG), the most abundant catechin-based flavonoid in green tea leaves, has significant antioxidant, anti-carcinogenic, antimicrobial, and neuroprotective properties. EGCG, given its low molecular weight and hydrophilic properties, can cross the blood-retinal barrier and is able to reach different ocular tissues such as the lens, cornea, and retina. EGCG has been shown to provide retinal protection against ischemia; sodium nitroprusside-, N-methyl-D-aspartate-, lipopolysaccharide-, light-, sodium iodate-, or H2O2-induced damage and diabetic retinopathy. This suggests that systemic EGCG administration has the potential to protect against retinal degenerative or neurodegenerative diseases such as RP. The aim of this work was to investigate whether EGCG can protect against RP progression in the animal P23H line 1, the model of RP. Albino P23H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical features of RP. Pigmented P23H rats were treated via intraperitoneal injection with saline or EGCG at a dose of 25 mg/kg every week from P100 to P160 and then compared to wild-type Long Evans rats. Rats treated with EGCG showed better visual and retinal electrical function with increased contrast sensitivity and b-wave values compared with those observed in P23H rats treated with vehicle. EGCG reduced lipid peroxidation and increased total antioxidant capacity and catalase and superoxide dismutase activities. No differences were observed in visual acuity, nitrate levels, nitrite levels or glutathione S-transferase activity. In conclusion, EGCG not only reduced the loss of visual function in P23H rats but also improved the levels of antioxidant enzymes and reduced oxidative damage. This study was approved by the Institutional Animal Care and Use Committee (CEICA) from the University of Zaragoza under project license PI12/14 on July 11, 2014.
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SIGNIFICANCE: Ocular light exposure therapy has been used in optometric therapies to improve binocular anomalies such as accommodative or vergence dysfunctions, amblyopia therapy or to increase the visual field. Currently, syntonic phototherapy is used worldwide by behavioral optometrists, vision trainers, or occupational therapists, among others, although these treatments are supported by only a few research studies that lack consensus on the efficacy of this approach. PURPOSE: In this article, we highlight the optical characteristics of lamps without evaluating the efficacy of their use in optometric procedures. METHODS: Our work analyzes four devices often used in clinical practice in terms of spectral power distribution, illuminance levels at the corneal plane, and both theoretical photopic and melanopic contributions to the visual system. RESULTS: First, illuminance levels reaching the corneal plane depend on the characteristics of each lamp and their distance from where the eye should be positioned; for example, delta-theta filter photopic illuminance is 13.1, 93.7, 22.7, or 41.6 lux with the four evaluated devices. Second, filters or modes named the same differ in terms of their spectral power distribution. Third, substantial difference in color appearance has been found among the same configurations. CONCLUSIONS: The spectral and iluminance characteristics of syntonic systems used for vision therapy vary widely, including variations among filters with the same identifying characteristics. This provides significant sources of variability, which limit the ability to conduct evidence-based medicine clinical trials to assess the true efficacy of syntonic therapy. This study furthers our knowledge of syntonic phototherapy from a technical perspective; however, longitudinal research examining patients' evolution pre-lighting and post-lighting treatments is required to justify and understand the effects of light exposure and its impact on optometric and ocular parameters more clearly.
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Acomodación Ocular , Colorimetría , Ojo , Humanos , Fototerapia , Visión OcularRESUMEN
Dedifferentiation is a loss of phenotypic specialization that converts differentiated cells into adult stem cells in order to proliferate and differentiate into replacement tissue. This occurs in several tissues from various organs, such as smooth muscle cells (SMCs) of the mammalian gastrointestinal tract. The aim of this study was to describe ultrastructural and immunohistochemical changes in SMCs which could be compatible with a dedifferentiation process in human and rabbit intestinal muscles. Ultrastructural study and immunohistochemical staining (SMemb and MyoD) on human and rabbit duodenum tissue sections were performed. In both species, this dedifferentiation process is characterized by a loss of intercellular junctions, increased intercellular spaces, cytoskeletal disorganization, perinuclear accumulation of large vacuoles that tend to fuse, rupture of the vacuole membrane and release of cytoplasmic fragments. Dedifferentiated cells show the characteristic phenotype of a mesenchymal cell with scarce perinuclear cytoplasm, long cytoplasmic prolongations and finely distributed granular chromatin in the nucleus. These morphological changes are accompanied by a modulation to a less mature phenotype showing immunoreactivity for the embryonic form of the myosin heavy chain and for the myogenic regulatory factor MyoD. We suggest that SMC dedifferentiation includes the elimination of the contractile apparatus, the activation of the nucleus and the re-expression of embryonic markers. We described an ultrastructural dedifferentiation process possible in intestinal SMCs. This dedifferentiation process seems to play a key role in the homeostasis of the intestinal muscle.
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Desdiferenciación Celular/fisiología , Duodeno/citología , Intestinos/citología , Células Madre Mesenquimatosas/citología , Proteína MioD/inmunología , Miocitos del Músculo Liso/ultraestructura , Cadenas Pesadas de Miosina/inmunología , Anciano , Animales , Variación Biológica Poblacional , Humanos , Inmunohistoquímica , Miocitos del Músculo Liso/inmunología , Conejos , Uniones Estrechas/fisiologíaRESUMEN
Retinitis pigmentosa (RP) comprises a group of inherited retinal degenerative conditions characterized by primary degeneration of the rod photoreceptors. Increased oxidative damage is observed in the retina, aqueous humor, and plasma of RP animal models and patients. The hepatic oxidative status may also be affected in RP due to oxidative damage influencing soluble macromolecules exiting the retina or to alterations in the melanopsin system resulting in chronic circadian desynchronization that negatively alters the oxidative stress defense system. P23H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical conditions of RP. We measured hepatic malondialdehyde and 4-hydroxyalkenal concentrations as oxidative stress markers; nitrite level as a total nitrosative damage marker; total antioxidant capacity; and the activities of catalase, superoxide dismutase (SOD), and glutathione S-transferase. Retinal visual function was assessed based on optomotor and electroretinogram responses. P23H transgenic rats exhibited diminished visual acuity, contrast sensitivity, and electroretinographic responses according to the level of retinal degeneration. P23H rats at 30 days of age already demonstrated only 47% of the hepatic total antioxidant capacity of wild-type animals. Hepatic catalase and SOD activities were also reduced in P23H rats after 120 days, but we detected no difference in glutathione S-transferase activity. P23H rats had increased hepatic oxidative and nitrosative damage markers. GSH/GSSG ratio showed a significant diminution in P23H rats at P120 compared to WT. We conclude that the liver is under increased oxidative stress in P23H rats. Further studies are required, however, to clarify the contribution of systemic oxidative damage to the pathogenesis of RP.
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Antioxidantes/metabolismo , Hígado/metabolismo , Estrés Oxidativo/fisiología , Degeneración Retiniana/metabolismo , Animales , Radicales Libres/metabolismo , Ratas , Ratas Long-Evans , Ratas Sprague-Dawley , Ratas Transgénicas , Degeneración Retiniana/complicaciones , Degeneración Retiniana/patología , Retinitis Pigmentosa/complicaciones , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/patología , RodopsinaRESUMEN
PURPOSE: To characterize the relationship between fundus autofluorescence (FAF), Optical Coherence Tomography (OCT) and immunohistochemistry (IHC) over the course of chronic retinal degeneration in the P23H rat. METHODS: Homozygous albino P23H rats, Sprague-Dawley (SD) rats as controls and pigmented Long Evans (LE) rats were used. A Spectralis HRA OCT system was used for scanning laser ophthalmoscopy (SLO) imaging OCT and angiography. To determine FAF, fluorescence was excited using diode laser at 488 nm. A fast retina map OCT was performed using the optic nerve as a landmark. IHC was performed to correlate with the findings of OCT and FAF changes. RESULTS: During the course of retinal degeneration, the FAF pattern evolved from some spotting at 2 months old to a mosaic of hyperfluorescent dots in rats 6 months and older. Retinal thicknesses progressively diminished over the course of the disease. At later stages of degeneration, OCT documented changes in the retinal layers, however, IHC better identified the cell loss and remodeling changes. Angiography revealed attenuation of the retinal vascular plexus with time. CONCLUSION: We provide for the first time a detailed long-term analysis of the course of retinal degeneration in P23H rats using a combination of SLO and OCT imaging, angiography, FAF and IHC. Although, the application of noninvasive methods enables longitudinal studies and will decrease the number of animals needed for a study, IHC is still an essential tool to identify retinal changes at the cellular level.