ABSTRACT
Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Müller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP.
Subject(s)
Antioxidants/therapeutic use , Melatonin/therapeutic use , Photoreceptor Cells, Vertebrate/drug effects , Retinitis Pigmentosa/drug therapy , Animals , Antioxidants/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Ependymoglial Cells/drug effects , Gliosis/prevention & control , Melatonin/pharmacology , Mice , Microglia/drug effectsABSTRACT
BACKGROUND: The objective of the study was to delineate clinical characteristics, surgical interventions, anatomic and visual outcomes of ruptured eye balls after trauma, and establish the prognostic indicators, which can assist clinicians in making correct surgical decisions during globe exploration for ruptured eyes. DESIGN: The study design used was a multicentre prospective cohort study, including six university-affiliated tertiary hospitals. PARTICIPANTS: We selected 242 cases of ruptured globe from the Eye Injury Vitrectomy Study database, until 31 December 2012. METHODS: All selected cases underwent vitreoretinal surgery, enucleation or evisceration, and were followed up for at least 6 months. Age, visual acuity (VA) after injury, ocular trauma zone, time to surgery, corneal laceration, scleral wound, extrusion of iris or lens, ciliary body damage, intraocular haemorrhage, retinal detachment or defect, proliferative vitreoretinopathy (PVR) and choroidal damage were the predisposing factors evaluated by logistic regression models. MAIN OUTCOME MEASURES: We compared the pre-surgical indicators between cases of anatomically restored eyes with VA of 4/200 or better, or eyes with initial no light perception restored light perception or better, and cases of VA worse than 4/200, silicone oil-sustained eyes, phthisis or enucleation. RESULTS: Nearly 40% of cases with ruptured globe were anatomically restored through vitreoretinal surgery. The closed-funnel retinal detachment or extensive retinal loss (odds ratio [OR] = 3.38, P = 0.026), PVR-C (OR = 3.45, P = 0.008), and choroidal damage (OR = 4.20, P = 0.004) were correlated with poor outcomes. CONCLUSION: The closed-funnel retinal detachment or extensive retinal loss, PVR-C, and choroidal damage are the risk factors for unfavourable outcomes in globe ruptures.
Subject(s)
Eye Injuries, Penetrating/diagnosis , Eye Injuries, Penetrating/surgery , Orbit/injuries , Vitrectomy , Vitreoretinal Surgery , Adolescent , Adult , Aged , Child , Child, Preschool , Eye Enucleation , Eye Evisceration , Female , Humans , Infant , Male , Middle Aged , Prognosis , Prospective Studies , Rupture , Visual Acuity/physiologyABSTRACT
Open globe injury is a common cause for blindness. Injured eyes with no light perception (NLP) should not be enucleated before exploratory vitrectomy. Some NLP eyes may attain light perception or better vision through the vitrectomy. The decision of enucleation should be determined during exploratory vitrectomy. The timing of vitrectomy in the open globe injury still has controversy, but more surgeons agreed that vitrectomy should be performed within 2 weeks after open globe injury. The deadline of timing of vitrectomy is 4 weeks after injury. Retinectomy around the edge of the wound and retinal re-attachment surgery are the key points to prevent proliferative vitreoretinopathy resulted from the injury.
Subject(s)
Eye Injuries, Penetrating/surgery , Humans , Prognosis , VitrectomyABSTRACT
Porous cryptomelane-type Mn oxide (OMS-2) has an outstanding redox property, making it a highly desirable substitute for noble metal catalysts for CO oxidation, but its catalytic activity still needs to be improved, especially in the presence of water. Given the strong structure-performance correlation of OMS-2 for oxidation reactions, herein, OMS-2 is synthesized by solid state (OMS-2S), reflux (OMS-2R), and hydrothermal (OMS-2H) methods, aiming to improve its CO oxidation performance through manipulating synthesis parameters to tailor its particle size, morphology, and crystallinity. Characterization shows that OMS-2S has the highest CO oxidation activity in the absence of water due to its low crystallinity, high specific surface area, large oxygen vacancy content, and good redox property, but the presence of water can greatly reduce its CO oxidation activity. Doping Cu into an OMS-2 can not only improve its CO oxidation activity but also greatly improve its water tolerance. The Cu-doped OMS-2S catalyst with â¼4 wt % Cu can achieve a T90 of 49 °C (1% CO/10% O2/N2 and WHSV = 60,000 mL·g-1·h-1), ranking among the lowest reported T90 values for Mn oxide-based CO oxidation catalysts, and it can maintain nearly 100% CO conversion in the presence of 5 vol % water for over 50 h. In situ DRIFTs characterization indicates that the good water resistance of Cu-doped OMS-2S can be attributed to the significantly suppressed surface hydroxyl group generation because of Cu doping. This work demonstrates the importance of the synthesis method and Cu doping in determining the CO oxidation activity and water resistance of OMS-2 and will provide guidance for synthesizing highly active and water-resistant CO oxidation catalysts.
ABSTRACT
Targeted therapy has expanded our current treatment options for various diseases including Langerhans cell histiocytosis. However, side effects associated with targeted therapy should be recognized and addressed. In this study, we report a pediatric bilateral pan-uveitis associated with the use of trametinib for Langerhans cell histiocytosis. A 10-year-old boy with Langerhans cell histiocytosis that was being treated by trametinib presented with mutton-fat keratic precipitates, anterior chamber cells, hyperemic swelling discs, subretinal fluid, and choroidal edema in both eyes. He was diagnosed with pan-uveitis in both eyes. When the trametinib therapy was stopped, the symptoms disappeared after local and systematic corticosteroid treatment. In conclusion, MEK (mitogen-activated protein/extracellular signal-related kinase kinase) inhibitor trametinib treatment alone might be associated with ocular toxicity presenting as Vogt Koyanaki Harada syndrome-like pan-uveitis. Ocular symptoms and signs should be monitored carefully during MEK inhibitor therapy.
ABSTRACT
Background: Cataract is the leading cause of blindness worldwide. In order to achieve large-scale cataract screening and remarkable performance, several studies have applied artificial intelligence (AI) to cataract detection based on fundus images. However, the fundus images they used are original from normal optical circumstances, which is less impractical due to the existence of poor-quality fundus images for inappropriate optical conditions in actual scenarios. Furthermore, these poor-quality images are easily mistaken as cataracts because both show fuzzy imaging characteristics, which may decline the performance of cataract detection. Therefore, we aimed to develop and validate an antiinterference AI model for rapid and efficient diagnosis based on fundus images. Materials and Methods: The datasets (including both cataract and noncataract labels) were derived from the Chinese PLA general hospital. The antiinterference AI model consisted of two AI submodules, a quality recognition model for cataract labeling and a convolutional neural networks-based model for cataract classification. The quality recognition model was performed to distinguish poor-quality images from normal-quality images and further generate the pseudo labels related to image quality for noncataract. Through this, the original binary-class label (cataract and noncataract) was adjusted to three categories (cataract, noncataract with normal-quality images, and noncataract with poor-quality images), which could be used to guide the model to distinguish cataract from suspected cataract fundus images. In the cataract classification stage, the convolutional-neural-network-based model was proposed to classify cataracts based on the label of the previous stage. The performance of the model was internally validated and externally tested in real-world settings, and the evaluation indicators included area under the receiver operating curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). Results: In the internal and external validation, the antiinterference AI model showed robust performance in cataract diagnosis (three classifications with AUCs >91%, ACCs >84%, SENs >71%, and SPEs >89%). Compared with the model that was trained on the binary-class label, the antiinterference cataract model improved its performance by 10%. Conclusion: We proposed an efficient antiinterference AI model for cataract diagnosis, which could achieve accurate cataract screening even with the interference of poor-quality images and help the government formulate a more accurate aid policy.
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PURPOSE: To delineate anatomic and visual outcomes of injured eye globes with perforating, and to develop the prognostic indicators for perforating eyes. METHODS: The case series study, from a multicenter prospective cohort database. To the date of December 31st, 2018, of 63 perforating globes were selected. All cases underwent vitreoretinal surgeries or enucleations, and were followed up for at least 6 months. Demographic characteristics, basic examination for traumatized eyes, and intraocular tissue damages were recorded by surgery-in-chief. At the follow-up visit, best corrected VA, intraocular pressure, the intraocular tamponade material, retinal anatomic outcome of eye-globes, and phthisis or enucleation were evaluated. RESULTS: Fifty injured eyes (79%) were caused by sharp objects and 13 eyes (21%) were injured by a missiles. Twenty-two injured eyes can be anatomically restored with final vision of more than 4/200 through vitreoretinal surgery. The PVR-C (OR = 5.67, P = 0.01), area of retinectomy more than 2 times of optic disk (OR = 5.16, P = 0.04), and macular damage (OR = 6.38, P = 0.01) were correlated with unfavorable outcomes. CONCLUSION: The injured eyes with perforation can be saved through vitreoretinal surgery, the PVR-C, retinectomy more than 2 times of optic disk, and macular damage were independent risk factors for poor long-term prognosis.
Subject(s)
Eye Injuries , Retinal Detachment , Eye Injuries/surgery , Humans , Prognosis , Prospective Studies , Retrospective Studies , Visual Acuity , VitrectomyABSTRACT
PURPOSE: To explore the clinical features, surgical interventions and prognosis of injured eyes following explosion and to develop the risk factors for poor prognosis. METHODS: A nested case-control study. To the date of 31 December 2018, 99 explosion-related eye globes were selected from the Eye Injury Vitrectomy Study database, which is a multicenter prospective cohort study and began in 1990s. All cases selected underwent vitreoretinal surgery or enucleation and were followed up for at least 6 months. Clinically meaningful preoperative variables and outcomes were used to develop logistic regression models. RESULTS: The unfavourable outcomes were defined as silicone oil-filled eyes, phthisis bulbi, enucleation and anatomically restored eyes whose final BCVA is worse than initial vision after 6 months of follow-up. The proportion of unfavourable outcomes was 92.0%, 60.9% and 66.7% in large festive fireworks, detonator and beer bottle groups respective. The anatomic and visual outcome of injured eyes with combined injury of blast wave and projectile were worse than that of ruptured eyes (Fisher's exact = 0.041). The extrusion of iris/lens (OR = 3.20, p = 0.015), PVR-C (OR = 6.08, p = 0.036) and choroid damage (OR = 5.84, p = 0.025) is independent risk factors of unfavourable prognosis for explosion-related eye trauma. CONCLUSION: The extrusion of iris/lens, PVR-C and choroid damage is the independent risk factors for unfavourable outcomes in explosion-related eye trauma. There is a unique injury mechanism in explosion-related eye trauma. SUMMARY STATEMENT: Through the nested case-control study, the extrusion of iris/lens, PVR-C, and choroid damage are the independent risk factors for unfavorable outcomes in explosion-related eye trauma. The mechanism of open globe mixture and close globe mixture in explosion-related eye trauma need more cases and participating units to explore together in the future.
Subject(s)
Explosions , Eye Injuries, Penetrating/complications , Retinal Detachment/surgery , Visual Acuity , Vitrectomy/methods , Adolescent , Adult , Aged , Case-Control Studies , Child , Child, Preschool , Eye Injuries, Penetrating/surgery , Female , Humans , Infant , Male , Middle Aged , Prognosis , Prospective Studies , Retinal Detachment/etiology , Young AdultABSTRACT
BACKGROUND: The relationship of gastric cancer to the presence of interleukin-8 (IL-8) 251 T/A has been reported with conflicting results. AIM: To further explore the association of IL-8 251 allele polymorphism with gastric cancer susceptibility. METHODS: We performed an extensive search of relevant studies and carried out a meta-analysis, including ten studies with 2,195 gastric cancer cases and 3,505 controls, to obtain a more precise estimate. RESULTS: The combined results based on all studies showed that the IL-8 251 allele AA genotype was a risk factor for gastric cancer [AA versus TT: odds ratio (OR) = 1.363, 95% confidence interval (CI): 1.199-1.527]. In subgroup analysis, a clear effect of AA in IL-8 251 allele was shown in Asians (AA versus TT: OR = 1.593, 95% CI: 1.013-2.173) but not in Caucasians or Mexicans. When stratified by Lauren classification, we found that the IL-8 251 allele TA and AA polymorphism was significantly associated with the diffuse type of gastric cancer (TA versus TT: OR = 1.448, 95% CI: 1.177-1.720; AA versus TT: OR = 1.586, 95% CI: 1.128-2.044). The IL-8 251 AA genotype was found to be a risk factor for cardiac gastric cancer (AA versus TT: OR = 1.840, 95% CI: 1.112-2.568) but not for noncardiac gastric cancer. CONCLUSIONS: This meta-analysis suggested that IL-8 251 allele A>T polymorphism might be a risk factor for gastric cancer.
Subject(s)
Genetic Predisposition to Disease/epidemiology , Interleukin-8/genetics , Polymorphism, Genetic , Stomach Neoplasms/genetics , Alleles , Case-Control Studies , Female , Gene Expression Regulation, Neoplastic , Humans , Incidence , Male , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Risk Assessment , Stomach Neoplasms/epidemiology , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Survival AnalysisABSTRACT
PURPOSE: The purpose of this study was to assess the contribution of sodium orthovanadate (SOV)-induced phosphatase inhibition to the activation of rat retinal pigment epithelium (RPE) cells. METHODS: Confluent cultures of rat RPE cells were treated with the general phosphatase inhibitor SOV. The effects of SOV on the cell cycle were determined by flow cytometry and protein detection of cyclin A and cyclin D1, two different cell cycle regulatory factors. The effects of SOV on cell differentiation were confirmed by immunostaining for α-smooth muscle actin (α-SMA). A migration assay was used to evaluate the effects of SOV on cell migration. RESULTS: SOV could accelerate the cell cycle of RPE cells. Western blotting showed that SOV significantly increased the expression of cyclin A and cyclin D1 in a dose-dependent fashion. The results of α-SMA staining and western blotting demonstrated that SOV induced RPE cells to differentiate toward better contractility and motility. The migration assay indicated that SOV improved the migration activity of RPE cells. CONCLUSIONS: Sodium orthovanadate can improve proliferation, differentiation, and migration of rat RPE cells and can also induce the reentry of contact-inhibited rat RPE cells into the cell cycle.
Subject(s)
Enzyme Inhibitors/pharmacology , Phosphoric Monoester Hydrolases/antagonists & inhibitors , Retinal Pigment Epithelium/drug effects , Vanadates/pharmacology , Actins/metabolism , Animals , Cell Cycle/drug effects , Cell Movement/drug effects , Cells, Cultured , Cyclin A1/metabolism , Cyclin D1/metabolism , Flow Cytometry , Fluorescent Antibody Technique, Indirect , Immunoenzyme Techniques , Male , Rats , Rats, Sprague-Dawley , Retinal Pigment Epithelium/enzymology , Retinal Pigment Epithelium/pathologyABSTRACT
OBJECTIVE: To research the Mn(2+) toxicity in vivo rabbit retina. Mn(2+) is used as a tracer in MRI. METHODS: It was an experimental study. Sixty pigmented rabbits (120 eyes) were divided into 5 groups randomly. Manganese chloride solution 25 µl of 10, 15, 20, 30, 40 mmol/L were injected intravitreally in one eye of each rabbit respectively as 5 experimental groups (n = 12). The saline (0.9%) 25 µl was injected intravitreally in other eye of each rabbit as control group (60 eyes). After intravitreal injections, all eyes were examined by color fundus camera, fluorescein angiography, flash electroretinography, light microscopy, and transmission electron microscopy on the 0(th), 7(th), and 28(th) day. RESULTS: On the 7(th) day after intravitreal injection, the average of the F-ERG b-wave amplitude was reduced significantly from 337 µV to 189 µV in the group of 15 mmol/L (F = 20.43, P < 0.05), but the amplitude was returned to normal on the 28(th) day. On the 7(th) day after intravitreal injections, the F-ERG b-wave amplitude was reduced significantly in the group of ≥ 20 mmol/L, and the amplitude was not returned to normal on the 28(th) day. There were abnormal changes in the structure of the retina in ≥ 20 mmol/L group at difference time after intravitreal injections. CONCLUSION: MnCl(2) as a tracer in vivo optic nerve, the concentration of ≤ 15 mmol/L caused only reversible changes in retinal function; The concentration of ≥ 20 mmol/L appears, damages in retinal function and morphology appeared.
Subject(s)
Chlorides/toxicity , Contrast Media/toxicity , Retina/drug effects , Animals , Chlorides/administration & dosage , Intravitreal Injections , Manganese Compounds/administration & dosage , Rabbits , Retina/pathology , Retina/physiopathologyABSTRACT
BACKGROUND: In recent years, artificial neural network is advocated in modeling complex multivariable relationships due to its ability of fault tolerance; while decision tree of data mining technique was recommended because of its richness of classification arithmetic rules and appeal of visibility. The aim of our research was to compare the performance of ANN and decision tree models in predicting hospital charges on gastric cancer patients. METHODS: Data about hospital charges on 1008 gastric cancer patients and related demographic information were collected from the First Affiliated Hospital of Anhui Medical University from 2005 to 2007 and preprocessed firstly to select pertinent input variables. Then artificial neural network (ANN) and decision tree models, using same hospital charge output variable and same input variables, were applied to compare the predictive abilities in terms of mean absolute errors and linear correlation coefficients for the training and test datasets. The transfer function in ANN model was sigmoid with 1 hidden layer and three hidden nodes. RESULTS: After preprocess of the data, 12 variables were selected and used as input variables in two types of models. For both the training dataset and the test dataset, mean absolute errors of ANN model were lower than those of decision tree model (1819.197 vs. 2782.423, 1162.279 vs. 3424.608) and linear correlation coefficients of the former model were higher than those of the latter (0.955 vs. 0.866, 0.987 vs. 0.806). The predictive ability and adaptive capacity of ANN model were better than those of decision tree model. CONCLUSION: ANN model performed better in predicting hospital charges of gastric cancer patients of China than did decision tree model.
Subject(s)
Decision Trees , Hospital Charges/trends , Models, Theoretical , Neural Networks, Computer , Stomach Neoplasms/economics , Adult , Female , Forecasting/methods , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Herpes virus is considered to be the pathogen of acute retinal necrosis (ARN) infection. Previous studies have found that patients with ARN caused by the varicella-zoster virus (VZV) are often older, and patients with herpes simplex virus (HSV) induced ARN are considerably younger. However, in our clinical work, we find that VZV is also a pathogen in younger ARN patients. We, therefore, aimed to analyze the common etiology of younger ARN patients. METHODS: A retrospective analysis was made of 20 eyes (18 patients) diagnosed as having ARN in the Department of Ophthalmology of Peking Union Medical College Hospital from 2014 to 2016. All patients were reviewed for demographic data, clinical course, clinical manifestations, time from onset to initial physician visit, duration of follow-up, visual acuity at both presentation and final visit, and treatment strategies. A paired t test was used to compare visual acuity between the presenting vision and those of final follow-up. Vitreous or aqueous specimens from 18 eyes of 18 patients were analyzed with multiplex polymerase chain reaction (mPCR)/quantitative PCR (qPCR) and xTAG-liquid chip technology (xTAG-LCT) to determine the causative virus of ARN. RESULTS: Final best visual acuity (BCVA) improved significantly from 1.36â±â0.95 (median 20/400) to 0.95â±â0.82 (median 20/100) (tâ=â2.714, Pâ=â0.015) after systemic and intravitreal antiviral treatment combined with or without pars plana vitrectomy. PCR and xTAG-LCT results showed four of the five samples in the younger group (32.2â±â5.2 years) and 12 of the 13 samples in the senior group (53.6â±â4.9 years) were positive for VZV, and two of the five samples in the younger group were positive for HSV-1. CONCLUSIONS: This study demonstrates that VZV is also a common causative virus for ARN in younger patients. Considering this finding, a systemic antiviral treatment protocol should be immediately changed to intravenous ganciclovir when the patient does not respond to acyclovir before determining the causative virus, especially in younger patients.
Subject(s)
Herpesvirus 3, Human/pathogenicity , Retinal Necrosis Syndrome, Acute/etiology , Retinal Necrosis Syndrome, Acute/virology , Adult , Age Factors , Female , Humans , Male , Middle Aged , Retinal Necrosis Syndrome, Acute/physiopathology , Retrospective Studies , Varicella Zoster Virus Infection/complications , Visual Acuity/physiologyABSTRACT
INTRODUCTION: To date, clinically available expanded polytetrafluoro-ethylene (ePTFE) vascular grafts are suboptimal for reconstructing small caliber (D < 6 mm) arteries, owing to thrombosis in early and restenosis in late stage. Our aim in this preliminary study was to fabricate a nano-fibrous vascular graft which was biofunctionalized with VEGF165 and heparin. The short term performance was evaluated both in vitro and in vivo. METHOD: Four-mm caliber grafts were prepared by the coaxial-elctrospun technique, which consisted of poly(l-lactide-co-caprolactone) [P(LLA-CL)] collagen and elastin. Heparin and endothelial cell growth factor-165 (VEGF165) were encapsulated in the core of the fibrous. Controlled release of the heparin and VEGF165 were evaluated for 28 days. Endothelial cells were cultured on the electrospun grafts or ePTFE grafts as controls. The cellular adhesion, proliferation and morphology were examined. Electrospun or ePTFE grafts were randomly implanted into a rabbit infrarenal aortic replacement model (n = 30) for 28 days without any antiplatelet therapy. At the termination, all grafts were examined by Doppler ultrasound and then evaluated with histology and scanning electron microscopy. RESULTS: The cumulative release amount of heparin (6.93 ± 1.03 mg) and VEGF165 (22.17 ± 5.56 µg) during 28 days were measured. Endothelial cells cultured on electrospun grafts showed significantly higher attachment efficiency and proliferation compared to the ePTFE ones (P < 0.001). At 2 h more ECs had attached to the P(LLA-CL)/Collagen/Elatin grafts (83.26 ± 8.02%) compared to P(LLA-CL) (67.07 ± 4.16%) and ePTFE (46.87 ± 8.85%). ECs proliferated faster on VEGF loaded grafts (O.D = 2.9 ± 1.2, n = 12) compared to ePTFE (O.D = 1.7 ± 1.0, n = 12). The patency was significantly higher in electrospun grafts (86.6%) than ePTFE grafts (40.0%) (P = 0.021). Correspondingly, the microscope images of electrospun implants showed little thrombus when compared with the ePTFE implants. CONCLUSION: Biofunctionalized electrospun graft showed surgical properties, hemocompatibility and higher short-term patency compared with the ePTFE grafts. Despite good early performances, profound study should be designed for long-term evaluation.
Subject(s)
Anticoagulants/administration & dosage , Blood Vessel Prosthesis , Heparin/administration & dosage , Postoperative Complications/prevention & control , Thrombosis/prevention & control , Vascular Endothelial Growth Factor A/administration & dosage , Animals , Aorta, Abdominal/transplantation , Biocompatible Materials , Collagen/chemistry , Elastin , Endothelial Cells/physiology , Polyesters , Postoperative Complications/etiology , Rabbits , Thrombosis/etiology , Vascular Grafting/adverse effects , Vascular Grafting/methodsABSTRACT
Axonal tracing is useful for detecting optic nerve injury and regeneration, but many commonly used methods cannot be used to observe axoplasmic flow and synaptic transmission in vivo. Manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) can be used for in vivo longitudinal tracing of the visual pathway. Here, we explored the dose response and time course of an intravitreal injection of MnCl2 for tracing the visual pathway in rabbits in vivo using MEMRI. We found that 2 mM MnCl2 enhanced images of the optic nerve but not the lateral geniculate body or superior colliculus, whereas at all other doses tested (5-40 mM), images of the visual pathway from the retina to the contralateral superior colliculus were significantly enhanced. The images were brightest at 24 hours, and then decreased in brightness until the end of the experiment (7 days). No signal enhancement was observed in the visual cortex at any concentration of MnCl2. These results suggest that MEMRI is a viable method for temporospatial tracing of the visual pathway in vivo. Signal enhancement in MEMRI depends on the dose of MnCl2, and the strongest signals appear 24 hours after intravitreal injection.
ABSTRACT
BACKGROUND: Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI. METHODS: Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. RESULTS: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. CONCLUSIONS: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.
Subject(s)
Magnetic Resonance Imaging/methods , Manganese/pharmacology , Administration, Topical , Animals , Aqueous Humor/drug effects , Aqueous Humor/metabolism , Cornea/drug effects , Cornea/metabolism , Epithelium, Corneal/drug effects , Epithelium, Corneal/metabolism , Male , Manganese/administration & dosage , Manganese/pharmacokinetics , Rabbits , Visual Pathways/drug effects , Vitreous Body/drug effects , Vitreous Body/metabolismSubject(s)
Contact Lenses , Silicones , Suture Techniques , Vitrectomy/instrumentation , Vitrectomy/methods , Equipment Design , HumansABSTRACT
OBJECTIVE: To Investigate the effectiveness and complications of injection of tissue plasminogen activator into a retinal vein for treatment of retinal vein occlusion via micropuncture of the retinal vein. METHODS: Thirty miniature pigs (one eye of each pig) were produced photodynamic thrombi of retinal vein by injecting Rose bengal (20 mg/kg) into the ear vein, and randomly divided into three groups: 1. control (n = 8), 2. infusion of sterile water (n = 8) or 3. infusion of tissue-type plasminogen activator (n = 14) in obstructed retinal vein. In the first group no micropuncture of retinal vein was performed. In the others micropuncture of retinal vein were performed by a micromanipulator that we designed and sterile water was infused in retinal vein in the second group or tissue-type plasminogen activator was infused in the third one. Fluorescent angiography and histological study were performed to document the morphological alterations with clinical observations. RESULTS: 18 eyes were successfully performed micropuncture of retinal vein in the 22 eyes (81.4%). Except stopping operation due to surgical accident, there were 7 eyes that the thrombi were lysed in 9 eyes by infusion of tissue-type plasminogen activator in obstructed retinal vein (77.8%). If the micropipette was not accurate for puncturing the vessels, the vessels' wall could be ruptured and hemorrhage appeared. If thrombi of retinal veins were lysed, no bleeding and no leakage of the infused drug were observed from the site of micropuncture after micropipette was withdrawn from the vessel. Sterile water failed to flush the clot downstream. When the thrombus failed to be dislodged, the infusion fluid would back flow into the distal retinal vein and, an exudative retinal detachment would occur. In the first group, the retina exhibited hemorrhages and edema due to the vein occluded. In the second group, sterile water resulted in exaggerated retinal edema and exudative retinal detachment. In the third group, after thrombi of retinal veins were lysed, the hemorrhages and edema of retinal tissues were reduced significantly in few days. CONCLUSIONS: Infusing thrombolytic agents into the thrombosed retinal vein is a new method for treatment of retinal vein occlusion. This surgery must performed accurately by a special design. This study demonstrated that the rate and dose of thrombolytic agents infused in retinal vein should be limited in case of injuring retina tissues.
Subject(s)
Punctures , Retinal Vein Occlusion/therapy , Tissue Plasminogen Activator/administration & dosage , Animals , SwineABSTRACT
OBJECTIVE: To develop a new photochemical method of experimental retinal vein occlusion and investigate the morphologic and histologic changes in the retina. METHODS: After intravenous injection of rose Bengal, the vessels next to the disc of miniature pigs in the experiment group (n = 15) were exposed to an endo-illuminator for 15 minutes. As a control group, the vessels next to the disc of each pig were exposed to the endo-illuminator without rose Bengal injection. After complete vascular occlusion, the eyes were observed at following times: one hour, and 1, 3, 7, 14, 21, and 28 days. After the 28th day, the eyes were enucleated and prepared for light and electron microscope examination. RESULTS: Histopathologic features were consistent with changes of retinal vein occlusion and formation of retinal vein thrombi was reliable. CONCLUSIONS: Photodynamic method combined with endo-illuminator was a simple, reliable and definitive experimental technique to produce retinal vein occlusion.
Subject(s)
Disease Models, Animal , Retinal Vein Occlusion/pathology , Swine, Miniature , Animals , Female , Male , Photochemotherapy/adverse effects , Retinal Vein Occlusion/etiology , Rose Bengal/adverse effects , SwineABSTRACT
In this case series of 74 patients with coexisting vitreoretinal injury and severe corneal opacification, after temporary keratoprosthesis (TKP) assisted pars plana vitrectomy (PPV), an allograft corneal transplant was not performed at the same time; instead, the patient's trephined corneal button was sutured back. One year after the surgery, if intraocular pressure of the injured eyes was above 8 mmHg, removing silicone oil was attempted, and penetrating keratoplasty could be performed. Finally, 10 eyes (13.5%) were enucleated due to atrophia bulbi; 46 eyes (62.2%) were silicone-oil sustained; 15 eyes (20.3%) were anatomically restored; and 3 eyes (4.0%) experienced recurrent retinal detachment. These figures only demonstrate a small percentage of the injured eyes in our series, which have PKP indications. It is a practical option to suture back the patient's trephined cornea following a TKP assisted PPV; keratoplasty was reserved for selected cases.