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Objective To investigate the relationship between the development of terminal rectal ganglion and spinal cord/sacral abnormalities in boys with complex anorectal malformations(ARMs)in order to improve the understanding of rectal ganglion development abnormalities in ARMs patients.Methods A retrospective trial was conducted on the male patients with complex ARMs admitted to our hospital from 2015 to 2021.The terminal rectal specimens were taken from them during anoplasty.According to the findings on development of terminal rectal ganglion after HE staining,the patients were classified into G1 group(ganglion cells observed)and G2 group(no ganglion cells observed).Imaging techniques were used to evaluate whether there were abnormalities in the spinal cord and sacrum,and their correlation with the terminal rectal ganglion development was analyzed.Results A total of 139 patients were enrolled,and their median age at anoplasty was 5.77(4.57,6.97)months.There were no significant differences between the G1(n=80,57.6%)and G2(n=59,42.4%)groups in ARMs pathological type(P=0.706)and age at surgery(P=0.140).Radiological findings showed there were 48 cases(34.5%)of spinal cord anomalies(SCA),25 cases(18.0%)of sacral abnormalities and 18 cases(12.9%)of coccyx abnormalities.No significant differences were observed in the incidences of SCA and sacral abnormalities between the G1 and G2 groups(P<0.05).Moreover,the differences of fatty filum terminale and syrinx were statistically significant(P<0.05).In addition,the ratio of sacrum to coccyx between the G1 and G2 groups were 0.72±0.10 vs 0.67±0.12(P<0.05)of the anteroposterior position and 0.77±0.09 vs 0.72±0.09(P<0.05)of the lateral position.Multivariate logistic regression analysis showed that sacral abnormalities,fatty filum terminale and syrinx were independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.Conclusion The development of terminal rectal ganglia in male patients with ARMs is closely associated with the abnormalities of spinal cord and sacrum.Sacral abnormalities,fatty filum terminale and syrinx are independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.
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Prostatic mesenchymal tumours are extremely uncommon benign tumors and very few cases have been published. Our case presented with diarrhea and increased urinary frequency with normal serum PSA levels. On multi-parametric MRI diffusely enlarging prostate with loss of zonal anatomy with possibility of inflammatory etiology was suggested. Trus guided biopsies were reviewed, which followed by immunohistochemistry aided in the diagnosis of ganglioneuroma. Surgical resection represents the only choice for both diagnosis and treatment. Because of the benign nature of ganglioneuroma, adjuvant chemo or radiotherapy is not indicated but regular follow-up is necessary for an early risk of potential local recurrence. Prostatic ganglioneuroma is the first case being reported to the best of our knowledge. The aim of the study was to document a newly diagnosed entity at this site and segregate more literature about it.
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La tomografía de coherencia óptica se ha convertido en el sistema de imagen más común para detectar de manera precoz el daño glaucomatoso; de ahí que resulte imprescindible para las decisiones clínicas y como criterio de inclusión en investigaciones y ensayos clínicos. El objetivo es exponer los avances en la aplicación de la tomografía de coherencia óptica en la detección del glaucoma a través de la revisión de las publicaciones de los últimos cinco años. La búsqueda se realizó en Google Académico para lo cual se emplearon palabras clave. Las mejoras en la tecnología de dominio espectral y de fuente de barrido han permitido la segmentación de células ganglionares, el reconocimiento de la apertura de la membrana de Bruch como punto de referencia para el análisis de los parámetros del disco óptico y el desarrollo de la angiografía sin contraste. Para el diagnóstico de glaucoma se analizó la estructura en tres localizaciones (células ganglionares maculares, capa de fibras neuroretiniana peripapilar, anillo neuroretiniano y copa en el disco óptico) y el plexo vascular superficial en dos (parafoveal y peripapilar). Se recomienda chequear calidad y presencia de artefactos previo al análisis de los resultados; así como complementar estos resultados con el interrogatorio y hallazgos al examen oftalmológico, fundamentalmente mediante biomicroscopia de polo posterior, para minimizar posibilidad de errores diagnósticos. Es útil tener esto en cuenta, a pesar de que sea numerosa la cantidad de pacientes que acuden cada día a la clínica del glaucoma. Se señalan ventajas y limitaciones de los parámetros estructurales y vasculares en el diagnóstico de glaucoma(AU)
Optical coherence tomography has become the most common imaging system for early detection of glaucomatous damage; hence, it is essential for clinical decisions and as a criterion for inclusion in research and clinical trials. The objective is to present the advances in the application of optical coherence tomography in the detection of glaucoma by reviewing the publications of the last five years. The search was performed in Google Scholar using keywords. Improvements in spectral domain and scanning source technology have allowed the segmentation of ganglion cells, the recognition of Bruch's membrane aperture as a reference point for the analysis of optic disc parameters and the development of non-contrast angiography. For the diagnosis of glaucoma, the structure was analyzed in three locations (macular ganglion cells, peripapillary neuroretinal fiber layer, neuroretinal ring and optic disc cup) and the superficial vascular plexus in two (parafoveal and peripapillary). It is recommended to check quality and presence of artifacts prior to the analysis of the results; as well as to complement these results with the interrogation and findings on ophthalmologic examination, mainly by posterior pole biomicroscopy, to minimize the possibility of diagnostic errors. It is useful to keep this in mind, despite the large number of patients that come to the glaucoma clinic every day. Advantages and limitations of structural and vascular parameters in the diagnosis of glaucoma are pointed out(AU)
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Humans , Glaucoma/diagnosis , Tomography, Optical Coherence/methods , Review Literature as TopicABSTRACT
A brand-new class of photoreceptors has been identified in the past 20a: intrinsically photosensitive retinal ganglion cells(ipRGC). With melanopsin as its photopigment, ipRGCs transmit light signals to non-imaging brain regions like the suprachiasmatic nucleus(SCN)and the olivary pretectal nucleus(OPN)to regulate circadian photoentrainment and pupillary light reflex; a small portion of the signals are projected to brain imaging regions like the dorsal lateral geniculate nucleus(dLGN)and superior colliculus(SC), to participate in imaging vision. There are six different ipRGC subtypes(M1~M6), each with its own morphological and physiological characteristics. In addition to receiving signaling inputs from the rods and cones, ipRGCs also regulate retinal signals through chemical and electrical synapses and play important roles in visual signaling and visual development. It has been discovered that ipRGCs are implicated in several systemic and ocular illnesses. Overall, various aspects of ipRGC are reviewed including the discovery, general physiological properties, signaling, and the relationship with disease in this work.
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Maintaining the homeostasis of intracellular components degradation and recycling, autophagy is a critical control mechanism of cellular quality. It promotes the degradation of cell components to provide nutrients and energy for cellular metabolism in stress response. The retina is a light-sensitive tissue that transduces and processes visual images in the eye, and it has a high demand for substances and energy. Basal autophagy is essential for holding retinal homeostasis and the normal function of the visual system. Therefore, the latest studies that investigating the participation of autophagy in eye diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, retinal dystrophies, and retinal detachment were summarized, providing a theoretical basis for the future treatment of eye diseases by regulating autophagy.
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Objective:Glaucoma is a leading cause of irreversible blindness,and effective therapies to reverse the visual system damage caused by glaucoma are still lacking.Recently,the stem cell therapy enable the repair and regeneration of the damaged retinal neurons,but challenges regarding the source of stem cells remain.This study aims to investigate a protocol that allows the dedifferentiation of Müller cells into retinal stem cells,following by directed differentiation into retinal ganglion cells with high efficiency,and to provide a new method of cellular acquisition for retinal stem cells. Methods:Epidermal cell growth factor and fibroblast growth factor 2 were used to induce the dedifferentiation of rat retinal Müller cells into retinal neural stem cells.Retinal stem cells derived from Müller cells were infected with a Trim9 overexpression lentiviral vector(PGC-FU-Trim9-GFP),and the efficiency of viral infection was assessed by fluorescence microscopy and flow cytometry.Retinoic acid and brain-derived neurotrophic factor treatments were used to induce the differentiation of the retinal stem cells into neurons and glial cells with or without the overexpression of Trim9.The expressions of each cellular marker(GLAST,GS,rhodopsin,PKC,HPC-1,Calbindin,Thy1.1,Brn-3b,Nestin,Pax6)were detected by immunofluorescence,PCR/real-time RT-PCR or Western blotting. Results:Rat retinal Müller cells expressed neural stem cells markers(Nestin and Pax6)with the treatment of epidermal cell growth factor and fibroblast growth factor 2.The Thy1.1 positive cell rate of retinal stem cells overexpressing Trim9 was significantly increased,indicating their directional differentiation into retinal ganglion cells after treatment with retinoic acid and brain-derived neurotrophic factor. Conclusion:In this study,rat retinal Müller cells are dedifferentiated into retinal stem cells successfully,and Trim9 promotes the directional differentiation from retinal stem cells to retinal ganglion cells effectively.
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Aging is a degenerative process that leads to dysfunction and abnormalities of tissues and cells in vivo.In the retinal neural degenerative diseases associated with aging, retinal ganglion cells (RGCs) are injured and lose their function.Through interacting ways including energy generation disorders, oxidative stress damage, mitochondrial mutation accumulation, protein misfolding and aggregation, immune inflammatory response, lack of neurotrophic factors, insufficient blood flow, increased pressure difference across lamina cribrosa and sclerosis of connective tissues, the sensitivity of RGCs to damage factor might be increased, which plays an important role in the process of optic nerve injury and degeneration.Rejuvenation of RGCs is supposed to be the key to the treatment of neurodegenerative diseases such as glaucoma, which can reduce or even reverse the damage caused by aging and promote the regeneration of RGCs, providing new targets for protecting visual function.Therefore, the research on the role of aging in RGCs injury will provide a new direction for optic nerve protection strategies.From aging and RGCs damage as well as new ideas of RGCs rejuvenation, this paper reviews the role and significance of aging in RGCs damage.
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With the popularity of electronic devices and the increasing environmental light pollution, more attention has been paid to the damage caused by retinal light irradiation and its pathogenic effects in retinal pigment degeneration, age-related macular degeneration and other diseases.The types of light-retinal tissue reaction are mainly photothermal and photochemical, and the photochemical reaction produced by visible light is closely related to retinal diseases.The parameters of light irradiation include wavelength, energy density and duration, etc.The effect of light irradiation on retinal cells can be influenced by many external factors under different parameters.Many in vitro models of light irradiation on retinal cells have been established to study the mechanism of light irradiation, especially blue light on retinal pigment epithelial cells, photoreceptor cells and nerve cells.Light irradiation can cause oxidative stress, endoplasmic reticulum stress and mitochondrial damage in retinal cells, which activates autophagy and regulates apoptosis.Inflammasome activation and exosomes are also involved in the regulation of light-induced damage to retinal pigment epithelial cells.There are also studies on the potential therapeutic effect of different wavelength light sources on cells.This review discusses the differences in cellular and light irradiation parameters between different models with respect to experimental models of retinal light irradiation in terms of types of light-retinal tissue responses, light irradiation parameters commonly used in biological studies, and retinal pigment epithelium light irradiation models, retinal photoreceptor light irradiation models, and retinal ganglion cell light irradiation models.
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Primary or secondary death of retinal ganglion cells (RGC) is a common outcome in various optic neuropathies, often resulting in severe visual damage. The inherent characteristics of RGC include the continuous upregulation of intracellular growth-inhibitory transcription factors and the downregulation of growth-inducing transcription factors during cell differentiation. Additionally, the external inhibitory microenvironment following RGC damage, including oxidative stress, chronic inflammation, lack of neurotrophic factors, high expression of myelin proteins, and the formation of glial scars, all restrict axonal regeneration. Both intrinsic and extrinsic factors lead to the death of damaged RGC and hinder axonal regeneration. Various neuroprotective agents and methods attempt to promote neuroprotection and axonal regeneration from both intrinsic and extrinsic aspects, and well knowledge of these neuroprotective strategies is of significant importance for promoting the neuroprotective experimental research and facilitating its translation into clinical practice.
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In addition to visual field defects, occipital lobe injury can also cause fundus changes, such as retinal nerve fiber layer atrophy, ganglion cell complex atrophy and even optic nerve atrophy, and these fundus changes have a good correlation with the visual field defect site. It is considered to be caused by transneuronal retrograde degeneration (TRD) of retinal ganglion cells secondary to occipital lobe injury. These changes can be detected by means of optical coherence tomography, fundus examination, magnetic resonance imaging, etc. Among them, optical coherence tomography is more sensitive than other examinations. Here, the anatomical basis of TRD, case reports, pathogenesis, auxiliary examination, treatment and prognosis of TRD secondary to occipital lobe injury are reviewd.
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Objective:To observe the protective effect of etomidate (ET) on cultured retinal ganglion cells (RGC) with mechanical injury in vitro.Methods:New Sprague-Dawley rat RGC was cultured in vitro and identified by double immunofluorescent labeling of Thy1.1 and microtubule associated protein 2. The cultured primary cells were randomly divided into control group, RGC scratch group, ET low dose group (1 μmol/L), ET medium dose group (5 μmol/L) and ET high dose group (10 μmol/L). The RGC mechanical injury model was established by using iris knife to culture cells in RGC scratch group and ET group with different concentration. Seven days after modeling, the RGC survival rate of each group was detected by cell count Kit 8 proliferation assay. The apoptosis rate of RGC was detected by Annexin Ⅴ/propyl iodide double staining. Single factor analysis of variance was used to compare the groups. The pairwise comparison between groups was tested by the least significant difference method.Results:The survival rates of RGC in RGC scratch group, ET low dose group, ET medium dose group and ET high dose group were (72.60±2.97)%, (73.73±1.14)%, (79.19±1.79)% and (83.88±0.94)%, respectively. The RGC apoptosis rates of control group, RGC scratch group, ET low dose group, ET medium dose group and ET high dose group were (5.08±0.17)%, (18.67±1.24)%, (17.96±0.74)%, (15.11±0.56)% and (11.67±1.32)%, respectively. Comparison of RGC survival rate between groups: compared with RGC scratch group, the cell survival rate of ET low-dose group, ET medium-dose group and ET high-dose group was increased, and the difference between RGC scratch group and ET low-dose group was not statistically significant ( P=0.728); the differences between RGC scratch group, ET medium dose group and ET high dose group were statistically significant ( P<0.001); the difference between ET medium dose group and ET high dose group was statistically significant ( P=0.002). Comparison of apoptosis rate of RGC among groups: the apoptosis rate of RGC scratch group was significantly higher than that of control group, the difference was statistically significant ( P<0.001). Compared with RGC scratch group, the apoptosis rate of ET low-dose group, ET medium-dose group and ET high-dose group was decreased, and there was no statistical significance between RGC scratch group and ET low-dose group ( P=0.869). The differences of apoptosis rate between RGC scratch group, ET medium dose group and ET high dose group were statistically significant ( P<0.05). The difference of apoptosis rate between ET medium dose group and ET high dose group was statistically significant ( P=0.007). Conclusion:ET has neuroprotective effect on RGC cultured in vitro with mechanical injury, and the protective effect increases with the increase of ET dose in a certain range.
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AIM:To investigate the effects and mechanisms of curcumin on apoptosis of retinal ganglion cells(RGCs)in chronic ocular hypertension rats.METHODS:A total of 21 Spraque-Dawley(SD)rats were randomly divided into 3 groups with 7 rats in each group. The rat models of chronic ocular hypertension were established by cauterization of the superior scleral veins in the high intraocular pressure model group and the curcumin treatment group, and the sham operation group only cut the conjunctiva without the cauterization of the superior scleral veins; the rats in the curcumin treatment group were intragastrically treated with curcumin at a dose of 4mL/kg, and the rats in the sham operation group and the high intraocular pressure model group were treated with pure water at a dose of 4mL/kg for 3wk. After 3wk, HE staining was used to observe the morphological and pathological changes of retina, the number of RGCs and the thickness of ganglion cell layer(GCL)in each group of rats; TUNEL staining was used to observe the apoptosis of RGCs and retinal cells in each group of rats; the expression levels of glutamate-cysteine ligase modifier subunit(GCLM)and heme oxygenase-1(HO-1)in the retina of each group of rats were detected by real-time fluorescence quantitative PCR, immunohistochemical staining and Western blot.RESULTS:Compared with the sham operation group, the retinal morphology of rats in the high intraocular pressure model group and the curcumin treatment group was disorganized, the number of RGCs was reduced, the GCL was thinner, the apoptosis rate of RGCs and retinal cells increased, and the expression levels of GCLM and HO-1 increased. Compared with the high intraocular pressure model group, the retinal morphology of rats in the curcumin treatment group was basically normal, the number of RGCs increased, the GCL thickened, the apoptosis rate of RGCs and retinal cells decreased, and the expression levels of GCLM and HO-1 increased.CONCLUSION:Curcumin can inhibit the apoptosis of RGCs in the rat model of chronic ocular hypertension by up-regulating the expression of antioxidant genes GCLM and HO-1.
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Objective:To investigate the effect and mechanism of NOD-like receptor family pyrin domain containing 12 (NLRP12) knockdown on inflammatory factor levels and retinal injury in retinal ganglion cells (RGCs) of rats with high intraocular pressure.Methods:Seventy SPF adult male SD rats were selected and randomized into control group, high intraocular pressure (IOP) group, high IOP+ small interfering RNA negative control (siNC) group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ recombinant rat caspase-1 (rrcaspase-1) group, with 14 rats in each group.Rats in the control group were only treated with conjunctival incision in the right eye, and ocular hypertension model was established in the other four groups with external scleral vein cauterization.High IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group were injected with siNC, siNLRP12 and siNLRP12+ rrcaspase-1 reagent via the tail vein, respectively.The IOP of the right eye was measured at 1 day, 1, 2 and 3 weeks after the operation.Three weeks after the operation, the retinal structure was observed by hematoxylin-eosin staining, and the number of RGCs in each group was counted.RGCs were divided into control group, rrcaspase-1 group, siNC+ rrcaspase-1 group, siNLRP12+ rrcaspase-1 group.The cells in rrcaspase-1 group, siNC+ rrcaspase-1 group and siNLRP12+ rrcaspase-1 group were treated with rrcaspase-1, siNC+ rrcaspase-1 and siNLRP12+ rrcaspase-1 reagent for 24 hours, respectively.No treatment was given to the control group.The expression levels of NLRP12, caspase-1 and cleaved-caspase-1 proteins in RGCs and retinal tissue were detected by Western blot.The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat serum or cell culture supernatant were detected by enzyme-linked immunosorbent assay.The study protocol was approved by the Animal Ethics Committee of the First People's Hospital of Chenzhou (No.2020086).Results:Compared with control group, the IOP was higher in high IOP group at 1, 2 and 3 weeks after cauterization, and the differences were statistically significant (all at P<0.05). The retinal tissue was clear with the RGCs in a single layer arrangement in the control group.In the high IOP group and the high IOP+ siNC group, the RGCs layer was loose and the inner plexiform layer was thin.The inner plexiform layer was thickened in high IOP+ siNLRP12 group compared with high IOP group, and the RGCs layer was loose in the high IOP+ siNLRP12 group and the high IOP+ siNLRP12+ rrcaspase-1 group.The number of RGCs in control group, high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group was 119.31±23.25, 89.19±16.98, 88.87±13.92, 109.33±10.25 and 92.89±12.58, respectively, showing a statistically significant overall difference ( F=201.932, P<0.001). The number of RGCs was lower in the high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group than the control group, higher in the high IOP+ siNLRP12 group than the high IOP+ siNC group, and lower in the high IOP+ siNLRP12+ rrcaspase-1 group than the high IOP+ siNLRP12 group, and the differences were statistically significant (all at P<0.05). The relative expressions of caspase-1 and cleaved-caspase-1 proteins and the concentrations of TNF-α and IL-1β in the retinal tissue were higher in high IOP group, high IOP+ siNC group, high IOP+ siNLRP12 group and high IOP+ siNLRP12+ rrcaspase-1 group than control group, higher in high IOP+ siNLRP12 group than high IOP+ siNC group, and higher in high IOP+ siNLRP12+ rrcaspase-1 group than high IOP+ siNLRP12 group (all at P<0.05). Relative expression levels of caspase-1 and cleaved-caspase-1 protein were increased in rrcaspase-1 group and siNC+ rrcaspase-1 group compared with control group, and relative expression levels of NLRP12, caspase-1 and cleaved-caspase-1 protein were decreased in siNLRP12+ rrcaspase-1 group compared with control group (all at P<0.05). The relative mass concentrations of TNF-α and IL-1β were increased in rrcaspase-1 group, siNC+ rrcaspase-1 group and siNLRP12+ rrcaspase-1 group compared with the control group (all at P<0.05). Relative expression levels of NLRP12, caspase-1 and cleaved-caspase-1 proteins and relative mass concentrations of TNF-α and IL-1β in siNLRP12+ rrcaspase-1 group were lower than those in siNC+ rrcaspase-1 group (all at P<0.05). Conclusions:Knockdown of NLRP12 can reduce the inflammatory response and retinal injury induced by high IOP by inhibiting the activation of caspase-1.
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Retinal ganglion cells (RGCs) are final output neurons from the retina to the brain, which can transmit light signals and participate in image-forming vision (IFV) (image formation) and non-image-forming vision (NIFV) (non-image formation). Visual processing system not only transmits visual information of images, but also influences human physiological activities and behaviors by incoming optical signals, which is called NIFV.NIFV relies less on signals generated by conventional photoreceptor cells, but a special class of intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs are a subset of retinal ganglion cells that express melanopsin.The axons of the ipRGCs project to unique targets and modulate a broad range of NIFV behaviors, from basic physiological regulation (such as heart rate and pupil size) to more complex behavioral regulation (such as circadian rhythm) and even higher-level cognitive processes (such as anxiety and other emotions). NIFV circuit is an important response to light, and ipRGCs plays a vital role in NIFV circuit.This article reviewed the regulation of NIFV circuit in physiological activities and behaviors, summarized the relationship between the projections of ipRGCs to the NIFV function, and provided ophthalmologists with more knowledge of visual system.
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Aging is often accompanied by age-related cataract and concurrent degeneration in brain function and structure.Restoration of vision after cataract surgery not only improves visual function, but also affects brain function and structure.Cataract surgery can enhance the effective transmission of blue light by intrinsically photoreceptive ganglion cells, and increase the secretion of melatonin in vivo, thereby regulating biological rhythm and improving the cognitive level of patients.Melatonin can activate its related molecular pathways, such as Reelin, Notch signaling, etc., affecting the accumulation and deposition of β-amyloid protein, reducing neuronal apoptosis, and playing an important role in a variety of neurodegenerative diseases.Although clinical studies have confirmed that vision restoration after cataract surgery can partially reverse the decline in brain function and structure, the molecular mechanisms involved remain unclear.Based on the eye-brain relationship, this paper reviewed and discussed the effects of vision restoration after cataract surgery on brain function and structure and the potential molecular mechanism, so as to provide new ideas and methods for brain remodeling.
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Abstract Background: Hirschsprung's Disease (HD) is characterized by intestinal sub-occlusion and the absence of enteric ganglion cells. A rectal biopsy examination is performed to confirm the diagnosis. In a recent study, we demonstrated that the analysis of 60 sections of rectal mucosa and submucosa stained by H&E may ensure a 90% diagnostic accuracy. Although the need to analyze so many sections makes the process of reading the slides more time-consuming, this encouraged us to study their distribution in the healthy rectal submucosa, to simplify the diagnosis. Objectives: To develop a method that facilitates HD diagnosis by studying the distribution of ganglion cells in the submucosal plexus. Methods: Using the calretinin technique, we studied the distribution of plexuses in 60 fragments of rectal submucosa from 19 cadavers. After the study, the reading method created was used for diagnosis in 47 cases of suspected HD, using H&E staining. The accuracy was verified by comparing the results obtained with H&E to those obtained with the acetylcholinesterase technique, the golden standard in our laboratory. Results: The study of submucosal plexus distribution showed that just by examining the submucosal region every 20 µm, approximately, it is possible to locate a ganglionic plexus, and we have already been able to diagnose HD with 93% accuracy. Conclusion: The study of ganglion cell distribution enabled the creation of a simplified method for reading the slides. The method applied achieved good accuracy and it can be used as an alternative method in HD diagnosis.
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ABSTRACT Purpose: The study aimed to investigate the correlation between arterial hemodynamics measured by color Doppler ultrasonography and retinal microarchitecture parameters determined by spectral-domain optical coherence tomography (SD-OCT) in pseudoexfoliation glaucoma. Methods: This prospective study included 82 participants. Peripapillary retinal nerve fiber layer, ganglion cell inner plexiform layer, and ganglion cell complex values were measured. Ophthalmic artery and central retinal artery flows were evaluated with color Doppler ultrasonography, and resistivity index values were calculated. Results: The study included 47 controls and 35 pseudoexfoliation glaucoma cases. In pseudoexfoliation glaucoma group, mean peripapillary retinal nerve fiber layer and ganglion cell complex thickness were statistically significantly lower in all quadrants compared to controls (p<0.001). Resistivity index values of the ophthalmic and central retinal arteries were significantly higher in pseudoexfoliation glaucoma group than in the controls (p<0.001 and r=0.684). Resistivity index values of the ophthalmic and central retinal arteries with ganglion cell complex thickness correlated significantly. On the other hand, no significant relationship for retinal nerve fiber layer thickness was identified. Conclusions: Structural changes (ganglion cell complex and ganglion cell inner plexiform layer) in patients with pseudoexfoliation glaucoma and early glaucomatous loss showed a significant correlation with changes in ocular vascular hemodynamics. In cases where systemic vascular resistance is increased, ganglion cell complex and ganglion cell inner plexiform layer may not exactly reflect glaucoma state. In such cases, thickness changes in the retinal nerve fiber layer may give more realistic results regarding glaucoma. We have seen that pseudoexfoliation glaucoma-induced structural deterioration and increased resistance in ocular hemodynamics correlated with ganglion cell complex, but not retinal nerve fiber layer.
RESUMO Objetivo: Investigar a correlação entre a hemodinâmica arterial, medida pela ultrassonografia com Doppler colorido, e os parâmetros de microarquitetura da retina, determinados pela tomografia de coerência óptica de domínio espectral (SD-OCT) no glaucoma pseudoexfoliativo. Métodos: Foram incluídos 82 participantes neste estudo prospectivo. Foram medidos os valores da camada de fibras nervosas da retina peripapilar, da camada plexiforme interna de células ganglionares e do complexo de células ganglionares. Os fluxos da artéria oftálmica e da artéria central da retina foram avaliados com ultrassonografia por Doppler colorida e foram calculados os valores do índice de resistividade. Resultados: Foram incluídos no estudo 47 casos de controle e 35 casos de glaucoma pseudoexfoliativo. No grupo com glaucoma pseudoexfoliativo, a média da camada de fibras nervosas da retina peripapilar e a espessura do complexo de células ganglionares foram menores em todos os quadrantes em comparação com os controles, com significância estatística (p<0,001). Os valores do índice de resistividade das artérias oftálmica e central da retina foram significativamente maiores no grupo com glaucoma pseudoexfoliativo que nos controles (p<0,001 e r=0,684). Ao se compararem os valores do índice de resistividade das artérias oftálmica e central da retina com a espessura do complexo de células ganglionares, foi encontrada uma correlação significativa entre elas. Por outro lado, não detectamos uma relação significativa para a espessura da camada de fibras nervosas da retina. Conclusões: Alterações estruturais (complexo de células ganglionares, camada plexiforme interna de células ganglionares) em pacientes com glaucoma pseudoexfoliativo com perda glaucomatosa precoce mostraram uma correlação significativa com alterações na hemodinâmica vascular ocular. Nos casos em que a resistência vascular sistêmica é aumentada, o complexo de células ganglionares e a camada plexiforme interna de células ganglionares podem não refletir exatamente o estado do glaucoma. Nesses casos, alterações na espessura da camada de fibras nervosas da retina podem dar resultados mais realistas em relação ao glaucoma. Observou-se uma correlação da deterioração estrutural induzida pelo glaucoma pseudoexfoliativo e do aumento da resistência na hemodinâmica ocular com o complexo de células ganglionares, mas não com a camada de fibras nervosas da retina.
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Objetivo: Determinar las características clínico-epidemiológicas de los pacientes diagnosticados con lesiones compresivas de la vía visual anterior. Métodos: Se realizó un estudio descriptivo transversal durante el período comprendido entre mayo de 2018 y marzo de 2020 con 41 pacientes con diagnóstico de síndrome compresivo de la vía visual anterior atendidos en el Servicio de Neuroftalmología del Instituto Cubano de Oftalmología "Ramón Pando Ferrer". Resultados: La mayor frecuencia en cuanto a síntomas fue la disminución progresiva de la visión central. Se encontraron lesiones de tipo tumoral en 39 pacientes para el 95,1 por ciento. Los defectos hemianópticos se detectaron en el campo visual del 45 por ciento de la muestra y el 33 por ciento presentó disminución difusa de la sensibilidad retiniana. Conclusiones: La mayoría de los pacientes fueron del sexo femenino en edades medias de la vida. Predominaron las lesiones tumorales sobre las vasculares. Los macroadenomas de hipófisis y los meningiomas fueron las etiologías más frecuentes y el sitio de compresión más encontrado fue el quiasma óptico. Se detectó disminución del grosor del complejo de células ganglionares maculares en la tomografía de coherencia óptica de la mayoría de los enfermos(AU)
Objective: To determine the clinical-epidemiological characteristics of patients diagnosed with compressive lesions of the anterior visual pathway. Methods: A cross-sectional descriptive study was conducted during the period from May 2018 to March 2020 with 41 patients diagnosed with compressive syndrome of the anterior visual pathway attended at the Neurophthalmology Service of the Cuban Institute of Ophthalmology "Ramón Pando Ferrer". Results: The most frequent symptom was the progressive decrease of central vision. Tumor type lesions were found in 39 patients for 95.1 percent. Hemianoptic defects were detected in the visual field of 45 percent of the sample and 33 percent presented diffuse decrease of retinal sensitivity. Conclusions: The majority of patients were female at middle ages of life. Tumor lesions predominated over vascular lesions. Pituitary macroadenomas and meningiomas were the most frequent etiologies and the most frequent site of compression was the optic chiasm. Decreased thickness of the macular ganglion cell complex was detected in the optical coherence tomography of most of the patients(AU)
Subject(s)
Humans , Female , Middle Aged , Visual Pathways/injuries , Epidemiology, Descriptive , Cross-Sectional StudiesABSTRACT
Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (Gs) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca2+]i of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.
ABSTRACT
Hallmarks of the pathophysiology of glaucoma are oxidative stress and apoptotic death of retinal ganglion cells (RGCs). Ginkgo biloba extract (EGb) with multi-target, multi-pathway functions has been reported to exert positive pharmacological effects on oxidative stress and damaged RGCs. However, the ingredients and anti-apoptotic targets of EGb in the treatment of open-angle glaucoma (OAG) have not been fully elucidated. Therefore, in-depth analysis is necessary for further research. Ginkgo biloba-related and anti-apoptotic targets were identified and then combined to obtain the intersection, representing the potential anti-apoptotic targets of Ginkgo biloba. In addition, compound-anti-apoptotic target and OAG-target protein-protein interaction network were merged to obtain five core genes and compound-OAG-anti-apoptotic target protein-protein interaction network. Consequently, the active compounds and anti-apoptotic targets of Ginkgo biloba in the treatment of OAG were identified, namely luteolin, β-sitosterol, kaempferol, stigmasterol, quercetin, and p53, Bax, Bcl-2, Caspase-3 and Caspase-9, respectively. For the anti-apoptotic targets of Ginkgo biloba in the treatment of OAG, Gene Ontology (GO) and pathway analysis were executed to confirm the gene functions of Ginkgo biloba in antagonizing apoptosis of RGCs. The pathway enrichment was mainly involved in transcriptional activation of p53 responsive genes, activation of caspases and apoptotic processes. Finally, we confirmed the results of the network analysis by H2O2 treated RGC-5 cells in vitro. The results demonstrated that EGb protection can effectively diminish H2O2-induced apoptosis by inhibiting p53 acetylation, reducing the ratio of Bax/Bcl-2 and suppressing the expression of specific cleavage of Caspase-9 and Caspase-3.