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1.
Curr Med Sci ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967890

RESUMEN

OBJECTIVE: To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency. METHODS: A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives. The clinical feature analysis included the evaluation of visual acuity, intraocular pressure, slit-lamp anterior segment examination, fundus photography, and spectral domain optical coherence tomography. To identify the mutation responsible for aniridia, targeted next-generation sequencing was used as a beneficial technique. RESULTS: A total of 4 mutations were identified, consisting of two novel frameshift mutations (c.314delA, p.K105Sfs*33 and c.838_845dup AACACACC, p.S283Tfs*85), along with two recurring nonsense mutations (c.307C>T, p.R103X and c.619A>T, p.K207*). Complete iris absence, macular foveal hypoplasia, and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families, while corneal lesions, cataracts, and glaucoma exhibited heterogeneity both among the families and within the same family. CONCLUSION: In our study, two novel PAX6 mutations associated with aniridia were identified in Chinese families, which expanded the phenotypic and genotypic spectrum of PAX6 mutations. We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

2.
Curr Med Sci ; 44(2): 419-425, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619684

RESUMEN

OBJECTIVE: Autosomal recessive bestrophinopathy (ARB), a retinal degenerative disease, is characterized by central visual loss, yellowish multifocal diffuse subretinal deposits, and a dramatic decrease in the light peak on electrooculogram. The potential pathogenic mechanism involves mutations in the BEST1 gene, which encodes Ca2+-activated Cl- channels in the retinal pigment epithelium (RPE), resulting in degeneration of RPE and photoreceptor. In this study, the complete clinical characteristics of two Chinese ARB families were summarized. METHODS: Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing was performed on the probands to screen for disease-causing gene mutations, and Sanger sequencing was applied to validate variants in the patients and their family members. RESULTS: Two novel mutations, c.202T>C (chr11:61722628, p.Y68H) and c.867+97G>A, in the BEST1 gene were identified in the two Chinese ARB families. The novel missense mutation BEST1 c.202T>C (p.Y68H) resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1. Another novel variant, BEST1 c.867+97G>A (chr11:61725867), located in intron 7, might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators. CONCLUSION: Our findings represent the first use of third-generation sequencing (TGS) to identify novel BEST1 mutations in patients with ARB, indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes. The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Enfermedades Hereditarias del Ojo , Enfermedades de la Retina , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina , Bestrofinas/genética , Bestrofinas/metabolismo , Fenotipo
3.
Front Med (Lausanne) ; 11: 1344107, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576708

RESUMEN

Background: As the most common acute optic neuropathy in older patients, nonarteritic anterior ischemic optic neuropathy (NAION) presents with varying degrees of visual acuity loss and visual field defect. However, there is no generally accepted treatment for NAION. Objectives: To evaluate the efficacy and safety of platelet-rich plasma (PRP) for patients with acute NAION within 2 months. Design: A prospective, nonrandomized controlled trial. Methods: Twenty-five eyes of 25 patients were enrolled. Of them, 13 received anisodine hydrobromide and butylphthalide-sodium chloride injection continuously for 10 days as basic treatment in the control group, and 12 received two tenon capsule injections of PRP on a 10 days interval as an additional treatment in the PRP group. We compared the best-corrected visual acuity (BCVA) and capillary perfusion density (CPD) of radial peripapillary capillaries and the moth-eaten eara of the peripapillary superficial capillary plexus and deep capillary plexus at 1 day (D1) before the first PRP treatment and 7 days (D7), 14 days (D14), and 30 days (D30) after the first PRP injection. Ocular and systemic adverse effects were assessed. Results: In the PRP group, a better BCVA occurred at D30 (adjusted p = 0.005, compared with D1, recovered from 0.67 ± 0.59 to 0.43 ± 0.59), and a significant improvement in CPD was observed at D30 (adjusted p < 0.001, p = 0.027, p = 0.027, compared with D1, D7, D14, in sequence, the value was 35.97 ± 4.65, 38.73 ± 4.61, 39.05 ± 5.26, 42.71 ± 4.72, respectively). CPD at D7 in the PRP group was better than that in the control group (p = 0.043). However, neither BCVA nor the moth-eaten area index were significantly different (all p > 0.5) between the two groups. The main adverse effect was local discomfort resolved within 1 week, and no other systemic adverse events occurred. Conclusion: Tenon capsule injection of PRP was a safe treatment for AION and could improve capillary perfusion of the optic nerve head and might be helpful in increasing short-term vision in patients with acute NAION.

4.
Adv Ophthalmol Pract Res ; 3(3): 112-118, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37846360

RESUMEN

Purpose: To establish a comprehensive treatment strategy and evaluate the efficacy of combination of anti-vascular endothelial growth factor (VEGF) injection, pars plana vitrectomy (PPV), endoscopic pan-retinal photocoagulation (PRP), and endoscopic cyclophotocoagulation (ECP) surgery for neovascular glaucoma (NVG) patients. Methods: This retrospective study included 30 patients (30 eyes) who were suffering from NVG and treated with PPV & PRP & ECP (ECP group, 16 eyes), or Ahmed glaucoma valve implantation (Ahmed group, 14 eyes). The intraocular pressure (IOP), number of postoperative anti-glaucoma medications, best-corrected visual acuity (BCVA), successful rate of surgery, and postoperative complications were recorded and statistically analyzed at the time points of preoperative, 1-day, 1-month, 3-months, 6-months, and 12-months after operation. Results: An obvious reduction in IOP and number of postoperative anti-glaucoma medications were observed in both the ECP group and Ahmed group after operation (P â€‹< â€‹0.05), and the ECP group showed a significantly lower IOP compared to the Ahmed group at the 6-months (P â€‹= â€‹0.014) and 12-months (P â€‹= â€‹0.047) postoperative time points, while there was no significant difference of medication number between the two groups except for 1-day after surgery. The BCVA showed no marked difference between the two groups preoperatively and postoperatively (P â€‹> â€‹0.05), while it was significantly improved in ECP group at 3-months (P â€‹= â€‹0.001), 6-months (P â€‹= â€‹0.004), and 12-months (P â€‹= â€‹0.010) time points comparing with preoperative BCVA. The surgical success rates in ECP group were also slightly higher than Ahmed group. And the complications after operation showed no marked differences. Conclusions: The comprehensive treatment of PPV, endoscopic PRP, and ECP surgery for NVG patients after anti-VEGF injection can control IOP effectively and be friendly to patients' BCVA without obvious serious complications throughout a 12-months follow-up period.

5.
Ocul Immunol Inflamm ; : 1-8, 2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36863003

RESUMEN

PURPOSE: To analyze a case of acute retinal necrosis (ARN) associated with pseudorabies virus (PRV) infection and discusses the clinical characteristics of PRV-induced ARN (PRV-ARN). METHODS: Case report and literature review of ocular features in PRV-ARN. RESULTS: A 52-year-old female diagnosed with encephalitis presented with bilateral vision loss, mild anterior uveitis, vitreous opacity, occlusive retinal vasculitis, and retinal detachment in her left eye. The result of metagenomic next-generation sequencing (mNGS) indicated that both cerebrospinal fluids and vitreous fluid tested positive for PRV. CONCLUSION: PRV, a zoonosis, can infect both humans and mammals. Patients affected with PRV may experience severe encephalitis and oculopathy, and the infection has been associated with high mortality and disability. ARN is the most common ocular disease, which develops rapidly following encephalitis and is characterized by five figures: bilateral onset, rapid progression, severe visual impairment, poor response to systemic antiviral drugs, and an unfavorable prognosis.

6.
Int J Ophthalmol ; 15(12): 1915-1923, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36536961

RESUMEN

AIM: To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy (adCORD) patients from two Chinese families with cone-rod homeobox (CRX) mutation (p.R41W), and to explore the clinical heterogeneity of adCORD with CRX mutation (p.R41W). METHODS: Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members. Analysis of clinical features was performed by visual acuity, slit lamp examination, visual field examination, fundoscopy, autofluorescence and spectral domain optical coherence tomography. Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes. RESULTS: A CRX missense mutation c.121C>T was identified in all patients, resulting in an amino acid change from arginine acid to tryptophan (p.R41W). The patients presented with early onset, progressive and different severities with CORD. CONCLUSION: This is the first report of the clinical phenotype of CRX mutation (p.R41W) in Chinese families, and the mutation can lead to a wide range of various retinal phenotypes.

7.
Semin Ophthalmol ; 37(6): 767-773, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35862571

RESUMEN

PURPOSE: The present study assessed the treatment of and risk factors for suprachoroidal hemorrhage (SCH) and reported the outcomes of drainage surgery with vitrectomy in a consecutive series of patients. METHODS: Retrospective case series were carried out to investigate the clinical data of 12 eyes from 12 patients who underwent suprachoroidal hemorrhage drainage with vitrectomy surgery over a 10-year period (from 2010 to 2020). The records of these patients were analyzed, including ophthalmologic examination, ophthalmologic ultrasonography, surgical procedures, and outcome measurements. RESULTS: Twelve consecutive patients with a mean age of 56.5 years were studied. Intraocular surgery, high myopia, glaucoma, hypertension and anticoagulant therapy were the most common risk factors for SCH. All patients underwent external drainage and pars plana vitrectomy surgery. All of the patients were followed up for 10.2 months. Overall, the mean preoperative BCVA improved from 2.3 LogMAR to 1.7 LogMAR at the last follow-up visit (P = .041). CONCLUSIONS: The risk factors for SCH include high myopia, glaucoma, hypertension and anticoagulant therapy. Drainage of SCH with vitrectomy is a valuable approach in the management of SCH.


Asunto(s)
Hemorragia de la Coroides , Drenaje , Vitrectomía , Anticoagulantes , Hemorragia de la Coroides/cirugía , Drenaje/métodos , Glaucoma/cirugía , Humanos , Hipertensión/complicaciones , Persona de Mediana Edad , Miopía/cirugía , Estudios Retrospectivos , Agudeza Visual , Vitrectomía/métodos
8.
Mol Med Rep ; 21(3): 1071-1076, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31894284

RESUMEN

The aim of the present study was to explore the safety and effectiveness of radiofrequency ablation (RFA) of the ciliary body for the treatment of glaucoma. A glaucoma model was established in New Zealand white rabbits, which were then treated with RFA of the ciliary body, utilizing an XL­1­type RF meter developed by the Chinese PLA General Hospital. After treatment, general ocular investigation, including ocular pressure was carried out, the anterior chamber was imaged via ultrasound biomicroscopy, and the pathological changes were observed via hematoxylin and eosin (H&E) staining. It was determined that the glaucoma model was successfully established in the New Zealand white rabbit by inducing high intraocular pressure (IOP). After RFA treatment, ablation spots were observed but no clear anterior chamber reaction was found. The ablation group showed a steady and continuous decrease of IOP, which was significantly lower than the model group at days 3 and 7 (P<0.05). A sclera pathway was observed in the ablation site 1­day post­treatment, which had mostly recovered by day 7. H&E staining demonstrated shedding of the ciliary epithelium, and an unclear boundary between muscle layer and blood vessel at day 1. This had fully recovered by day 14, with clear ciliary layers and well­arranged muscle structures observed. The present study suggested that treatment with RFA could decrease IOP without substantial side effects in the glaucoma model in the rabbit. Therefore, it could be used as a strategy to control IOP and as a treatment for glaucoma in the clinic.


Asunto(s)
Cuerpo Ciliar/efectos de la radiación , Glaucoma/diagnóstico , Glaucoma/terapia , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ablación por Radiofrecuencia/métodos , Animales , Biopsia , Modelos Animales de Enfermedad , Femenino , Glaucoma/etiología , Inmunohistoquímica , Masculino , Conejos , Resultado del Tratamiento
9.
Oncotarget ; 8(37): 61551-61560, 2017 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-28977884

RESUMEN

Cellular Ca2+ signals play a critical role in cell physiology and pathology. In most non-excitable cells, store-operated Ca2+ entry (SOCE) is an important mechanism by which intracellular Ca2+ signaling is regulated. However, few drugs can selectively modulate SOCE. 2-Aminoethoxydiphenyl borate (2APB) and its analogs (DPB162 and DPB163) have been reported to inhibit SOCE. Here, we examined the effects of another 2-APB analog, DPB161 on SOCE in acutely-isolated rat submandibular cells. Both patch-clamp recordings and Ca2+ imaging showed that upon removal of extracellular Ca2+ ([Ca2+]o=0), rat submandibular cells were unable to maintain ACh-induced Ca2+ oscillations, but restoration of [Ca2+]o to refill Ca2+ stores enable recovery of these Ca2+ oscillations. However, addition of 50 µM DPB161 with [Ca2+]o to extracellular solution prevented the refilling of Ca2+ store. Fura-2 Ca2+ imaging showed that DPB161 inhibited SOCE in a concentration-dependent manner. After depleting Ca2+ stores by thapsigargin treatment, bath perfusion of 1 mM Ca2+ induced [Ca2+]i elevation in a manner that was prevented by DPB161. Collectively, these results show that the 2-APB analog DPB161 blocks SOCE in rat submandibular cells, suggesting that this compound can be developed as a pharmacological tool for the study of SOCE function and as a new therapeutic agent for treating SOCE-associated disorders.

10.
Front Cell Neurosci ; 11: 98, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28473754

RESUMEN

Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods.

11.
Sci Rep ; 7(1): 1011, 2017 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-28432360

RESUMEN

Following retinal degeneration, retinal remodeling can cause neuronal microcircuits to undergo structural alterations, which particularly affect the dendrites of bipolar cells. However, the mechanisms and functional consequences of such changes remain unclear. Here, we used Royal College of Surgeon (RCS) rats as a model of retinal degeneration, to study structural changes in rod bipolar cells (RBCs) and the underlying mechanisms of these changes. We found that, with retinal degeneration, RBC dendrites extended into the outer nuclear layer (ONL) of the retina, and the ectopic dendrites formed synapses with the remaining photoreceptors. This ectopic neuritogenesis was associated with brain-derived neurotrophic factor (BDNF) - expression of which was negatively regulated by miR-125b-5p. Overexpression of miR-125b-5p in the retinae of RCS rats diminished RBC ectopic dendrites, and compromised the b-wave of the flash electroretinogram (ERG). In contrast, down-regulation of miR-125b-5p (or exogenous BDNF treatment) increased RBC ectopic dendrites, and improved b-wave. Furthermore, we showed that the regulation of ectopic neuritogenesis by BDNF occurred via the downstream modulation of the TrkB-CREB signaling pathway. Based on these findings, we conclude that ectopic dendrites are likely to be providing functional benefits and that, in RCS rats, miR-125b-5p regulates ectopic neuritogenesis by RBCs through modulation of the BDNF-TrkB-CREB pathway. This suggests that therapies that reduce miR-125b-5p expression could be beneficial in human retinal degenerative disease.


Asunto(s)
Dendritas/metabolismo , MicroARNs/genética , Células Bipolares de la Retina/citología , Degeneración Retiniana/patología , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Modelos Animales de Enfermedad , Electrorretinografía , Humanos , Ratas , Células Bipolares de la Retina/patología , Degeneración Retiniana/genética , Células Fotorreceptoras Retinianas Bastones/citología , Células Fotorreceptoras Retinianas Bastones/patología
12.
Biosci Rep ; 36(1): e00289, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26802146

RESUMEN

Retinitis pigmentosa (RP) describes a group of inherited retinopathies that are characterized by the progressive degeneration of photoreceptor neurons, which causes night blindness, a reduction in the peripheral visual field and decreased visual acuity. More than 50 RP-related genes have been identified. In the present study, we analysed a Chinese family with autosomal recessive RP. We identified a compound heterozygous mutation, c.265delC and c.1537G>A, in CNGA1 using targeted next-generation sequencing (NGS) of RP-causing genes. The mutations were validated in the family members by Sanger sequencing. The mutations co-segregated with the RP phenotype and were absent from ethnically-matched control chromosomes. The mutant (mut) CNGA1 p.(G513R) protein caused by the mis-sense novel mutation c.1537G>A was expressed in vitro. The mut CNGA1 p.(G513R) protein was largely retained inside the cell rather than being targeted to the plasma membrane, suggesting the absence of cGMP-gated cation channels in the plasma membrane would be deleterious to rod photoreceptors, leading lead to RP.


Asunto(s)
Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética , Familia , Heterocigoto , Mutación Missense , Retinitis Pigmentosa/genética , Sustitución de Aminoácidos , Pueblo Asiatico , Femenino , Humanos , Masculino
13.
World Neurosurg ; 84(3): 756-65, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25957723

RESUMEN

BACKGROUND: This study investigated whether functional neuronavigation can be used to remove lesions in the lateral ventricle while preserving patients' neurologic functionality. METHODS: A total of 60 patients with lateral ventricular meningiomas were divided into study and control groups (n = 30 each). Diffusion tensor and blood oxygenation level-dependent functional magnetic resonance imaging were used for fiber tracking and eloquent cortex localization, respectively, in the study group. The surgical approach was based on coregistered data sets from 3-D lesion and brain structure reconstructions. Patients in the control group underwent anatomic neuronavigation-guided surgery. The patients' demographics, degree of resection, visual field, language score, movement, preoperative and postoperative Karnofsky Performance Status (KPS) scores, and surgical complications were recorded. RESULTS: Tumors were completely removed in both groups. Patients in the study group had a higher rate of visual field preservation than controls (P = 0.01). The two groups had similar motor and language functions after surgery, except that fewer cases of transient aphasia were observed in the former (P < 0.05). KPS scores for the study and control groups were 80 (70-80) and 70 (60-70), respectively (P < 0.01), at 2 weeks and 90 (80-100) and 85 (70-90), respectively (P = 0.022), at 3 months after surgery. CONCLUSIONS: Functional neuronavigation preserved neurologic functionality and was especially beneficial for protecting optical functionality and for the rapid recovery of patients.


Asunto(s)
Ventrículos Laterales/cirugía , Meningioma/cirugía , Neuronavegación/métodos , Procedimientos Neuroquirúrgicos/métodos , Lóbulo Occipital/cirugía , Lóbulo Parietal/cirugía , Cirugía Asistida por Computador/métodos , Adolescente , Adulto , Anciano , Imagen de Difusión Tensora , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Campos Visuales , Adulto Joven
14.
Genet Test Mol Biomarkers ; 19(1): 3-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25268471

RESUMEN

PURPOSE: The aim of this study is to examine whether or not myocilin (MYOC) genetic variations are associated with susceptibility to primary angle-closure glaucoma (PACG) in the Han Chinese population. METHODS: Four single-nucleotide polymorphisms (SNPs)-rs235913, rs183532, rs12076134, and rs235875-in the MYOC gene were genotyped in 212 adult patients with PACG and 255 age-, sex-, and ethnic-matched healthy controls by using a polymerase chain reaction-restriction fragment length polymorphism assay. Data were analyzed by chi-square analysis. RESULTS: The four SNPs in the MYOC gene were in the Hardy-Weinberg equilibrium in all the subjects. The frequencies of A allele rs183532 were significantly different between the PACG patients and the controls (0.238 vs. 0.169, p=0.008; OR=1.541; 95% CI: 1.117-2.127). The frequencies of the AA genotype and A allele of rs235913 were increased in PACG patients compared with controls, but the difference was not significant (p=0.037, p=0.017, respectively). A comparison of the distributions of the genotypes and alleles of rs12076134 and rs235875 showed no statistically significant differences between the PACG patients and the controls (p>0.05). Haplotype analysis indicated that the frequency of the AATG and AATA haplotypes was significantly higher for PACG patients than for control subjects (both p<0.001). However, the frequency of CGGA and CGTG haplotypes was lower for PACG patients than for control subjects (p<0.001). CONCLUSIONS: Our study suggests that rs183532 is associated with an increased risk of PACG in the Chinese Han population.


Asunto(s)
Alelos , Proteínas del Citoesqueleto/genética , Proteínas del Ojo/genética , Glaucoma de Ángulo Cerrado/genética , Glicoproteínas/genética , Haplotipos , Polimorfismo de Nucleótido Simple , Adulto , Pueblo Asiatico/etnología , China/etnología , Femenino , Glaucoma de Ángulo Cerrado/etnología , Humanos , Persona de Mediana Edad
15.
Lipids Health Dis ; 13: 156, 2014 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-25292258

RESUMEN

BACKGROUND: Diabetic retinopathy, the main microvascular complications of diabetes and one of the leading causes of blindness worldwide. Interesting reports on the role of inflammatory/proangiogenic high mobility group 1 (HMGB-1) cytokine and phospholipases A2 (PLA2) in neovascularization have diverted our concentration to reveal whether HMGB-1 and PLA2 plays role in diabetic retinopathy. METHODS: We performed our study in streptozotocin (STZ)-induced diabetic rat model. The expression levels of the cytokines, chemokines, and cell adhesion molecules in retinal tissues were evaluated by quantitative RT-PCR. HMGB-1 and PLA2 protein levels along with VEGF, TNF-α, IL-1ß and ICAM-1 levels were also measured. RESULTS: We observed the retinal pericytes, endothelial injury/death and breakdown of blood-retinal barrier (BRB). The protein expression of HMGB-1, PLA2 and IL-1ß were significantly increased in micro vessels from retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM-1 and TNF-α. Further investigation revealed that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate endothelial cell death. Similarly, increased expression of PLA2 represents the diabetic mediated alteration of BRB, perhaps up regulating the VEGF. CONCLUSIONS: Our data suggest that HMGB-1 and PLA2 involved in retinal pericyte and endothelial injury and cell death in diabetic retinopathy. From this study, we suggest that HMGB-1 and PLA2 may be interesting targets in managing diabetic retinopathy.


Asunto(s)
Diabetes Mellitus Experimental/enzimología , Retinopatía Diabética/enzimología , Proteína HMGB1/metabolismo , Fosfolipasas A2/metabolismo , Animales , Apoptosis , Quimiocinas/genética , Quimiocinas/metabolismo , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Diabetes Mellitus Experimental/complicaciones , Expresión Génica , Proteína HMGB1/genética , Masculino , Proteínas de la Membrana/metabolismo , Pericitos/enzimología , Fosfolipasas A2/genética , Ratas Sprague-Dawley , Células Ganglionares de la Retina/fisiología , Vasos Retinianos/enzimología , Vasos Retinianos/patología
16.
Cell Biochem Biophys ; 70(3): 1655-61, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25030406

RESUMEN

Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. Findings indicate that obtusifolin has antioxidant properties. The purpose of this study was to examine the effect of obtusifolin on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without obtusifolin (100, 200, and 400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of obtusifolin administration on retinal 8-hydroxy-2'deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked immunosorbent assay. Obtusifolin administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the four diabetic groups (with and without obtusifolin). Retinal 8-OHdG and nitrotyrosine levels were significantly increased, respectively, in diabetes, and obtusifolin administration inhibited these increases. Our results demonstrate that the long-term administration of obtusifolin has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. Obtusifolin represents an achievable adjunct therapy to help prevent vision loss in diabetic patients.


Asunto(s)
Antraquinonas/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Capilares/efectos de los fármacos , Retinopatía Diabética/patología , 8-Hidroxi-2'-Desoxicoguanosina , Administración Oral , Animales , Capilares/citología , Capilares/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/etiología , Hiperglucemia/patología , Masculino , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Retina/metabolismo , Retina/patología , Tirosina/análogos & derivados , Tirosina/metabolismo
17.
Int J Ophthalmol ; 6(2): 131-5, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23638410

RESUMEN

AIM: To investigate the role of heparanase-1 in laser-induced choroidal neovascularization (CNV). METHODS: Experimental CNV was induced by krypton laser photocoagulation in 15 male Brown Norway rats. Fundus fluorescein angiography and histopathological examination were performed in observing the CNV development. The expression and distribution of heparanase-1 protein in the laser lesions were determined by immunohistochemistry and western blotting analysis. RESULTS: The success rate of laser induced CNV was approximately 75% on 3-4 weeks after laser photocoagulation. The protein levels of heparanase-1 increased significantly in the retina-choroidal complex of CNV models when compared to normal rat eyes (P<0.01). Immunostaining confirmed strong heparanase-1 expressions in all laser lesions, and it displayed to be highest at the newly formed blood vessels within the fibrovascular complex in the subretinal space. CONCLUSION: Heparanase-1 is closely involved in the development of laser induced CNV.

18.
Mol Neurobiol ; 47(2): 833-44, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23329344

RESUMEN

Granule cell migration influences the laminar structure of the cerebellum and thereby affects cerebellum function. Bergmann glia are derived from radial glial cells and aid in granule cell radial migration by providing a scaffold for migration and by mediating interactions between Bergmann glia and granule cells. In this review, we summarize Bergmann glia characteristics and the mechanisms underlying the effect of Bergmann glia on the radial migration of granule neurons in the cerebellum. Furthermore, we will focus our discussion on the important factors involved in glia-mediated radial migration so that we may elucidate the possible mechanistic pathways used by Bergmann glia to influence granule cell migration during cerebellum development.


Asunto(s)
Movimiento Celular/fisiología , Cerebelo/citología , Cerebelo/crecimiento & desarrollo , Neuroglía/fisiología , Animales , Humanos , Neuroglía/citología , Transducción de Señal/fisiología
19.
Cell Mol Neurobiol ; 32(3): 467-475, 2012 04.
Artículo en Inglés | MEDLINE | ID: mdl-22297541

RESUMEN

Adeno-associated virus vector plasmid carrying the expression cassette of brain-derived neurotrophic factor (BDNF), pAAV-BDNF, was constructed and packaged into recombinant adeno-associated virus (rAAV-BDNF). The rAAV-BDNF was intravitreally injected into streptzotocin (STZ)-induced diabetic Sprague-Dawley (SD) Rats. Data showed that over-expression of BDNF could increase alive retinal ganglion cell (RGC) number and improve its function in streptzotocin(STZ)-induced diabetic rats, which might be a new method to treat diabetic neuropathy and retinopathy.

20.
Neurosurgery ; 69(5): 1070-84; discussion 1084, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21654536

RESUMEN

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) combined with optic radiation neuronavigation may be safer for resection of cerebral lesions involving the optic radiation. OBJECTIVE: To investigate whether iMRI combined with optic radiation neuronavigation can help maximize tumor resection while protecting the patient's visual field. METHODS: Forty-four patients with cerebral tumors adjacent to the optic radiation were enrolled in the study. The reconstructed optic radiations were observed so that a reasonable surgical plan could be developed. During the surgery, microscope-based fiber tract neuronavigation was routinely implemented. The lesion location (lateral or not to the optic radiation) and course of the optic radiation (stretched or not) were categorized, and their relationships to the visual field defect were determined. RESULTS: Analysis of the visible relationship between the optic radiation and the lesion led to a change in surgical approach in 6 patients (14%). The mean tumor residual rate for glioma patients was 5.3% (n = 36) and 0% for patients with nonglioma lesions (n = 8). Intraoperative MRI and fiber tract neuronavigation increased the average size of resection (first and last iMRI scanning, 88.3% vs 95.7%; P < .01). Visual fields after surgery improved in 5 cases (11.4%), exhibited no change in 36 cases (81.8%), and were aggravated in 3 cases (6.8%). CONCLUSION: Diffusion tensor imaging information was helpful in surgical planning. When iMRI was combined with fiber tract neuronavigation, the resection rate of brain lesions involving the optic radiation was increased in most patients without harming the patients' visual fields.


Asunto(s)
Neoplasias Encefálicas/cirugía , Cerebro/cirugía , Glioma/cirugía , Imagen por Resonancia Magnética/métodos , Neuronavegación/métodos , Vías Visuales/cirugía , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Cerebro/diagnóstico por imagen , Femenino , Glioma/diagnóstico por imagen , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Estudios Prospectivos , Radiografía , Dosificación Radioterapéutica , Vías Visuales/diagnóstico por imagen , Adulto Joven
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