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1.
Annu Rev Cell Dev Biol ; 31: 171-99, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26566111

RESUMO

If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation.


Assuntos
Bactérias/genética , Segregação de Cromossomos/genética , Cromossomos Bacterianos/genética , Animais , Proteínas de Bactérias/genética , Reparo do DNA/genética , Replicação do DNA/genética , Proteínas de Ligação a DNA/genética
2.
J Biol Chem ; 300(2): 105614, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159863

RESUMO

The activation and mobilization of immune cells play a crucial role in immunotherapy. Existing therapeutic interventions, such as cytokines administration, aim to enhance immune cell activity. However, these approaches usually result in modest effectiveness and toxic side effects, thereby restricting their clinical application. Protease-activated receptors (PARs), a subfamily of G protein-coupled receptors, actively participate in the immune system by directly activating immune cells. The activation of PARs by proteases or synthetic ligands can modulate immune cell behavior, signaling, and responses to treat immune-related diseases, suggesting the significance of PARs agonism in immunotherapy. However, the agonism of PARs in therapeutical applications remains rarely discussed, since it has been traditionally considered that PARs activation facilitates disease progressions. This review aims to comprehensively summarize the activation, rather than inhibition, of PARs in immune-related physiological responses and diseases. Additionally, we will discuss the emerging immunotherapeutic potential of PARs agonism, providing a new strategic direction for PARs-mediated immunotherapy.


Assuntos
Imunoterapia , Receptores Ativados por Proteinase , Peptídeo Hidrolases/metabolismo , Receptores Acoplados a Proteínas G , Receptores Ativados por Proteinase/agonistas , Receptores Ativados por Proteinase/metabolismo , Transdução de Sinais , Neoplasias/imunologia , Neoplasias/terapia , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/terapia , Humanos , Animais
3.
FASEB J ; 37(1): e22675, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36468684

RESUMO

Post-translational modification of G-protein coupled receptors (GPCRs) plays a central role in tissue hemostasis and cancer. The molecular mechanism of post-translational regulation of protease-activated receptors (PARs), a subgroup of GPCRs is yet understudied. Here we show that the cell-surface transmembrane E3 ubiquitin ligase ring finger 43 (RNF43) is a negative feedback regulator of PAR2 , impacting PAR2 -induced signaling and colon cancer growth. RNF43 co-associates with PAR2 , promoting its membrane elimination and degradation as shown by reduced cell surface biotinylated PAR2 levels and polyubiquitination. PAR2 degradation is rescued by R-spondin2 in the presence of leucine-rich repeat-containing G-protein-coupled receptor5 (LGR5). In fact, PAR2 acts jointly with LGR5, as recapitulated by increased ß-catenin levels, transcriptional activity, phospho-LRP6, and anchorage-independent colony growth in agar. Animal models of the chemically induced AOM/DSS colon cancer of wt versus Par2/f2rl1 KO mice as also the 'spleen-liver' colon cancer metastasis, allocated a central role for PAR2 in colon cancer growth and development. RNF43 is abundantly expressed in the Par2/f2rl1 KO-treated AOM/DSS colon tissues while its level is very low to nearly null in colon cancer adenocarcinomas of the wt mice. The same result is obtained in the 'spleen-liver' model of spleen-inoculated cells, metastasized to the liver. High RNF43 expression is observed in the liver upon shRNA -Par2 silencing. "Limited-dilution-assay" performed in mice in-vivo, assigned PAR2 as a member of the cancer stem cell niche compartment. Collectively, we elucidate an original regulation of PAR2 oncogene, a member of cancer stem cells, by RNF43 ubiquitin ligase. It impacts ß-catenin signaling and colon cancer growth.


Assuntos
Neoplasias do Colo , Receptor PAR-2 , Camundongos , Animais , Receptor PAR-2/genética , beta Catenina/genética , Células-Tronco Neoplásicas
4.
Am J Med Genet A ; 194(7): e63589, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38469956

RESUMO

PARS2 encodes an aminoacyl-tRNA synthetase that catalyzes the ligation of proline to mitochondrial prolyl-tRNA molecules. Diseases associated with PARS2 primarily affect the central nervous system, causing early infantile developmental epileptic encephalopathies (EIDEE; DEE75; MIM #618437) with infantile-onset neurodegeneration. Dilated cardiomyopathy has also been reported in the affected individuals. About 10 individuals to date have been described with pathogenic biallelic variants in PARS2. While many of the reported individuals succumbed to the disease in the first two decades of life, autopsy findings have not yet been reported. Here, we describe neuropathological findings in a deceased male with evidence of intracranial calcifications in the basal ganglia, thalamus, cerebellum, and white matter, similar to Aicardi-Goutières syndrome. This report describes detailed autopsy findings in a child with PARS2-related mitochondrial disease and provides plausible evidence that intracranial calcifications may be a previously unrecognized feature of this disorder.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Calcinose , Doenças Mitocondriais , Malformações do Sistema Nervoso , Humanos , Calcinose/genética , Calcinose/patologia , Masculino , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/patologia , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Doenças Mitocondriais/diagnóstico por imagem , Aminoacil-tRNA Sintetases/genética , Lactente , Mutação/genética , Diagnóstico Diferencial , Encéfalo/patologia , Encéfalo/diagnóstico por imagem
5.
J Exp Biol ; 227(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690647

RESUMO

Hibernation is an extreme state of seasonal energy conservation, reducing metabolic rate to as little as 1% of the active state. During the hibernation season, many species of hibernating mammals cycle repeatedly between the active (aroused) and hibernating (torpid) states (T-A cycling), using brown adipose tissue (BAT) to drive cyclical rewarming. The regulatory mechanisms controlling this process remain undefined but are presumed to involve thermoregulatory centres in the hypothalamus. Here, we used the golden hamster (Mesocricetus auratus), and high-resolution monitoring of BAT, core body temperature and ventilation rate, to sample at precisely defined phases of the T-A cycle. Using c-fos as a marker of cellular activity, we show that although the dorsomedial hypothalamus is active during torpor entry, neither it nor the pre-optic area shows any significant changes during the earliest stages of spontaneous arousal. Contrastingly, in three non-neuronal sites previously linked to control of metabolic physiology over seasonal and daily time scales - the choroid plexus, pars tuberalis and third ventricle tanycytes - peak c-fos expression is seen at arousal initiation. We suggest that through their sensitivity to factors in the blood or cerebrospinal fluid, these sites may mediate metabolic feedback-based initiation of the spontaneous arousal process.


Assuntos
Nível de Alerta , Plexo Corióideo , Células Ependimogliais , Hibernação , Proteínas Proto-Oncogênicas c-fos , Torpor , Animais , Cricetinae , Masculino , Tecido Adiposo Marrom/metabolismo , Nível de Alerta/genética , Plexo Corióideo/metabolismo , Células Ependimogliais/metabolismo , Hibernação/genética , Mesocricetus , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Torpor/genética
6.
Int J Legal Med ; 138(2): 467-486, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37775592

RESUMO

Age estimation is crucial when the state of personhood is a mitigating factor in the identification of immature human remains. The maturation sequence of immature bones is a valuable alternative to dental development and eruption standards. Bordering the foramen magnum and pars basilaris, the pars lateralis is somewhat understudied. The aim of this study was to comprehensively describe the morphology of the immature human pars lateralis bone. Human pars laterali were sourced from the crania of 103 immature individuals of unknown provenance from the Johannesburg Forensic Paediatric Collection (JFPC), University of the Witwatersrand (HREC-Medical: M210855). The study sample was subdivided into early prenatal (younger than 30 gestational weeks; n = 32), prenatal (30-40 gestational weeks, n = 41) and postnatal (birth to 7.5 months, n = 30) age groups. The morphology of the pars laterali was studied using a combination of bone mineral density pattern assessments, geometric morphometrics and stereomicroscopy. Bone mineral density in postnatal individuals was lower when compared with the prenatal individuals. No statistically significant differences between density points were noted. The overall shape of the pars lateralis changed from a triangular shape in the early prenatal individuals to a fan-like quadrilateral bone in postnatal individuals. The angulation of the medial border for the foramen magnum highlighted a change in shape between straight in the early prenatal cohort to V-shaped in the postnatal individuals. The various technical approaches used in the current study provided detailed descriptions of the pars lateralis which establishes a valuable foundation for diagnostic criteria employing morphological predictors for biological profiling.


Assuntos
Parte Reticular da Substância Negra , Gravidez , Feminino , Humanos , Criança , Densidade Óssea , África do Sul , Antropologia Forense
7.
J Pineal Res ; 76(5): e12986, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38965880

RESUMO

This contribution reviews the role of inbred and transgenic mouse strains for deciphering the mammalian melatoninergic and circadian system. It focusses on the pineal organ as melatonin factory and two major targets of the melatoninergic system, the suprachiasmatic nuclei (SCN) and the hypophysial pars tuberalis (PT). Mammalian pinealocytes sharing molecular characteristics with true pineal and retinal photoreceptors synthesize and secrete melatonin into the blood and cerebrospinal fluid night by night. Notably, neuron-like connections exist between the deep pinealocytes and the habenular/pretectal region suggesting direct pineal-brain communication. Control of melatonin biosynthesis in rodents involves transcriptional regulation including phosphorylation of CREB and upregulation of mPer1. In the SCN, melatonin acts upon MT1 and MT2 receptors. Melatonin is not necessary to maintain the rhythm of the SCN molecular clockwork, but it has distinct effects on the synchronization of the circadian rhythm by light, facilitates re-entrainment of the circadian system to phase advances in the level of the SCN molecular clockwork by acting upon MT2 receptors and plays a stabilizing role in the circadian system as evidenced from locomotor activity recordings. While the effects in the SCN are subtle, melatonin is essential for PT functions. Via the MT1 receptor it drives the PT-intrinsic molecular clockwork and the retrograde and anterograde output pathways controlling seasonal rhythmicity. Although inbred and transgenic mice do not show seasonal reproduction, the pathways from the PT are fully intact if the animals are melatonin proficient. Thus, only melatonin-proficient strains are suited to investigate the circadian and melatoninergic systems.


Assuntos
Ritmo Circadiano , Melatonina , Animais , Melatonina/metabolismo , Ritmo Circadiano/fisiologia , Camundongos , Modelos Animais , Núcleo Supraquiasmático/metabolismo , Camundongos Transgênicos , Glândula Pineal/metabolismo
8.
J Pineal Res ; 76(5): e12996, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39129720

RESUMO

In mammals, seasonal opportunities and challenges are anticipated through programmed changes in physiology and behavior. Appropriate anticipatory timing depends on synchronization to the external solar year, achieved through the use of day length (photoperiod) as a synchronizing signal. In mammals, nocturnal production of melatonin by the pineal gland is the key hormonal mediator of photoperiodic change, exerting its effects via the hypothalamopituitary axis. In this review/perspective, we consider the key developments during the history of research into the seasonal synchronizer effect of melatonin, highlighting the role that the pars tuberalis-tanycyte module plays in this process. We go on to consider downstream pathways, which include discrete hypothalamic neuronal populations. Neurons that express the neuropeptides kisspeptin and (Arg)(Phe)-related peptide-3 (RFRP-3) govern seasonal reproductive function while neurons that express somatostatin may be involved in seasonal metabolic adaptations. Finally, we identify several outstanding questions, which need to be addressed to provide a much thorough understanding of the deep impact of melatonin upon seasonal synchronization.


Assuntos
Mamíferos , Melatonina , Estações do Ano , Melatonina/metabolismo , Animais , Mamíferos/metabolismo , Fotoperíodo , Humanos , Glândula Pineal/metabolismo
9.
Brain Topogr ; 38(1): 9, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39422783

RESUMO

Chronotype is an inherent physiological trait reflecting an individual's subjective preference for their sleep awakening time, exerting a substantial influence on both physical and mental well-being. While existing research has established a close relationship between chronotype and individual brain structure, prior studies have predominantly focused on individual measurements of brain structural scales, thereby limiting the exploration of the underlying mechanisms of structural changes. This study seeks to validate previous research findings and enhance our understanding of the correlation between circadian rhythm preference and diverse cortical indicators in healthy young individuals. Magnetic resonance imaging (MRI) scans and chronotype assessments were conducted once for all participants, comprising 49 late chronotype (LC) young adults and 49 matched early chronotype young adults. The Chronotype Questionnaire was utilized to assess morningness and eveningness preferences. Surface-based analysis of structural MRI data revealed that LC young adults exhibited thinner cortical thickness of left pars orbitalis and lower cortical mean curve of right paracentral gyrus. Overall, this study represents a significant advancement in elucidating the connection between brain structure and function within the context of chronotypes.


Assuntos
Córtex Cerebral , Ritmo Circadiano , Imageamento por Ressonância Magnética , Sono , Humanos , Masculino , Adulto Jovem , Feminino , Imageamento por Ressonância Magnética/métodos , Ritmo Circadiano/fisiologia , Sono/fisiologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Córtex Cerebral/anatomia & histologia , Adulto , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Encéfalo/anatomia & histologia , Cronotipo
10.
Acta Pharmacol Sin ; 45(6): 1160-1174, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38438581

RESUMO

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4ß2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-ß-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.


Assuntos
Neurônios GABAérgicos , Hiperalgesia , Camundongos Endogâmicos C57BL , Receptores Nicotínicos , Animais , Receptores Nicotínicos/metabolismo , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/fisiologia , Masculino , Hiperalgesia/metabolismo , Hiperalgesia/tratamento farmacológico , Camundongos , Parte Reticular da Substância Negra/metabolismo , Parte Reticular da Substância Negra/efeitos dos fármacos , Nicotina/farmacologia , Analgésicos/farmacologia , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Capsaicina/farmacologia , Acetilcolina/metabolismo , Optogenética , Limiar da Dor/efeitos dos fármacos
11.
Cereb Cortex ; 33(7): 4085-4100, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36057839

RESUMO

Inferior frontal cortex pars opercularis (IFCop) features a distinct cerebral dominance and vast functional heterogeneity. Left and right IFCop are implicated in developmental stuttering. Weak left IFCop connections and divergent connectivity of hyperactive right IFCop regions have been related to impeded speech. Here, we reanalyzed diffusion magnetic resonance imaging data from 83 children (41 stuttering). We generated connection probability maps of functionally segregated area 44 parcels and calculated hemisphere-wise analyses of variance. Children who stutter showed reduced connectivity of executive, rostral-motor, and caudal-motor corticostriatal projections from the left IFCop. We discuss this finding in the context of tracing studies from the macaque area 44, which leads to the need to reconsider current models of speech motor control. Unlike the left, the right IFCop revealed increased connectivity of the inferior posterior ventral parcel and decreased connectivity of the posterior dorsal parcel with the anterior insula, particularly in stuttering boys. This divergent connectivity pattern in young children adds to the debate on potential core deficits in stuttering and challenges the theory that right hemisphere differences might exclusively indicate compensatory changes that evolve from lifelong exposure. Instead, early right prefrontal connectivity differences may reflect additional brain signatures of aberrant cognition-emotion-action influencing speech motor control.


Assuntos
Gagueira , Humanos , Gagueira/diagnóstico por imagem , Imageamento por Ressonância Magnética , Mapeamento Encefálico/métodos , Fala , Área de Broca
12.
Graefes Arch Clin Exp Ophthalmol ; 262(7): 2237-2246, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38363356

RESUMO

PURPOSE: To present the outcomes of pars plana vitrectomy (PPV) in patients with infectious, non-infectious, and unidentified uveitis, focusing on visual and clinical outcomes, diagnostic yield, and surgery-related complications. METHODS: This retrospective, single-center study included patients who underwent 23-gauge PPV for the management of uveitis and had at least 6 months of follow-up. Patients were divided into infectious, non-infectious, and unidentified uveitis groups based on definitive diagnosis after surgery. Etiologies of uveitis, indications for surgery, diagnostic yield, visual outcomes, presence of cystoid macular edema (CME), immunosuppressive drugs, intraoperative and postoperative complications, and repeated vitrectomies were reviewed. RESULTS: This study included 62 eyes of 54 patients. Twenty eyes were diagnosed with infectious uveitis, 24 eyes with non-infectious uveitis, and 18 eyes with unidentified uveitis. The diagnostic yield of vitrectomy was 41.7%. Mean BCVA significantly improved at postoperative 1 month compared to baseline and remained stable at following time-points in all groups. The most common early postoperative complication was increased intraocular pressure (17%), and late complication was cataract (36%). Nine eyes underwent re-vitrectomy and the most common cause was retinal detachment with proliferative vitreoretinopathy (PVR). CONCLUSION: PPV seems to be effective in diagnosing cases of unknown origin, improving visual acuity, and reducing the need for systemic immunosuppressive drugs. PVR is the most serious complication with poor prognosis that requires repeated surgery in patients with uveitis.


Assuntos
Uveíte , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Uveíte/diagnóstico , Adulto , Seguimentos , Idoso , Resultado do Tratamento , Adulto Jovem , Complicações Pós-Operatórias/diagnóstico , Adolescente
13.
Artigo em Inglês | MEDLINE | ID: mdl-39249514

RESUMO

PURPOSE: To evaluate the impact of temperature-controlled pars plana vitrectomy (PPV) on structural and functional outcomes in a rabbit eye model in vivo. METHODS: Ten healthy New Zealand White rabbits underwent temperature-controlled PPV in the right eye (group A), using a device specifically designed to heat the infusion fluid/air and integrated into the vitrectomy machine, and conventional PPV in the left eye (group B). Both eyes received ophthalmic examination and electroretinography (ERG) before and 1 week postoperatively. After 1-week ERG, rabbits were enucleated and then sacrificed. Histological and immunohistochemical examinations were performed on enucleated eyes and expression of glial fibrillary acidic protein (GFAP) and vimentin investigated. RESULTS: Postoperatively, only group B showed significantly decreased amplitude and increased latency of a-wave at 3 cd·s/m2 (p = 0.001 and 0.005, respectively). Significant increase of b-wave latency at 0.01 cd·s/m2 was detected in both groups (p = 0.019 and 0.023, respectively). Postoperatively, amplitude of oscillatory potentials (OPs) increased significantly in group A (p = 0.023) and decreased in group B. In both groups, OPs latency significantly increased at 1-week test (P < 0.05). A greater number of eyes without structural retinal alterations was detected in group A compared to group B (6 vs 5, respectively). GFAP expression was higher in group B than group A, even if the difference was not statistically significant. CONCLUSION: Temperature-controlled PPV resulted in more favorable functional and structural outcomes in rabbit eyes compared with conventional PPV, supporting the potential beneficial role of the intraoperative management of intraocular temperature in vitreoretinal surgery.

14.
Graefes Arch Clin Exp Ophthalmol ; 262(8): 2481-2489, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38530449

RESUMO

PURPOSE: To test the hypothesis that optical coherence tomography (OCT) choroidal hypertransmission width (CHW) is a prognostic biomarker in idiopathic macular hole (MH) surgery METHODS: Retrospective cohort study of consecutive patients undergoing successful pars plana vitrectomy for idiopathic MH. We collected demographic, clinical, and OCT variables at the preoperative and last available visits. Two investigators assessed the following OCT parameters: MH minimum diameter, base diameter, CHW, ellipsoid zone, and external limiting membrane status (absent vs. present). Delta CHW was calculated as the difference between CHW and MH minimum diameter. Linear models were used to investigate factors associated with postoperative best-corrected visual acuity (BCVA) and BCVA change. RESULTS: Thirty-six eyes (36 patients) with a median (interquartile range (IQR)) follow-up of 9 (8-11) months were included. The median BCVA (IQR) improved from 0.75 (1-0.6) logMAR preoperatively to 0.2 (0.6-0.1) logMAR at the last visit (p < 0.001). Preoperative MH minimum diameter (for a 10-µm increase, estimate (standard error (SE)): 0.009 (0.003) logMAR, p = 0.003), base diameter (for a 10-µm increase, 0.003 (0.001) logMAR, p = 0.032), CHW (for a 10-µm increase, 0.008 (0.002) logMAR, p < 0.001), and delta CHW (for a 10-µm increase, 0.013 (0.005) logMAR, p = 0.009) were significantly associated with postoperative BCVA. The proportion of variance explained was the highest for MH CHW (R2 0.35), followed by minimum MH diameter (R2 0.24), delta CHW (R2 0.19), and MH base diameter (R2 0.14). None of the study variables was associated with delta BCVA. CONCLUSION: Preoperative CHW is associated with postoperative visual acuity in patients undergoing successful idiopathic MH surgery and may be a useful OCT prognostic biomarker.


Assuntos
Corioide , Perfurações Retinianas , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Tomografia de Coerência Óptica/métodos , Perfurações Retinianas/cirurgia , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/fisiopatologia , Estudos Retrospectivos , Masculino , Feminino , Vitrectomia/métodos , Acuidade Visual/fisiologia , Corioide/diagnóstico por imagem , Prognóstico , Idoso , Seguimentos , Pessoa de Meia-Idade , Período Pós-Operatório , Biomarcadores
15.
Graefes Arch Clin Exp Ophthalmol ; 262(8): 2713-2724, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38407591

RESUMO

Lamellar macular holes (LMHs) are a manifestation of myopic tractional maculopathy (MTM). Owing to the complex and multidirectional traction force in the elongated eyeball, the clinical features, development, evolution, and treatment algorithms of LMH in highly myopic eyes may differ from those of idiopathic LMH or MTM in general. This review aimed to specifically explore the LMHs in highly myopic eyes. Several developmental processes of LMH and their association with macular retinoschisis have been demonstrated, with the tractional component identified in all processes. Epiretinal proliferation was more prevalent and more extensive in LMHs in highly myopic eyes than in idiopathic LMHs. LMHs in highly myopic eyes may remain stable or progress to foveal detachment and full-thickness macular hole with or without retinal detachment. The predictive factors associated with disease progression were summarized to facilitate monitoring and guide surgical intervention. The treatment of LMHs in highly myopic eyes was based on an algorithm for treating myopic tractional maculopathy, including gas tamponade, pars plana vitrectomy, macular buckling, and a combination of vitrectomy and macular buckling. New internal limiting membrane (ILM) manipulation techniques such as fovea-sparing ILM peeling or fovea-sparing ILM peeling combined with ILM flap insertion could reduce the risk of developing iatrogenic full-thickness macular holes postoperatively. Further research should focus on the treatment of LMH in highly myopic eyes.


Assuntos
Miopia Degenerativa , Perfurações Retinianas , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Perfurações Retinianas/cirurgia , Tomografia de Coerência Óptica/métodos , Miopia Degenerativa/complicações , Miopia Degenerativa/diagnóstico , Miopia Degenerativa/fisiopatologia , Vitrectomia/métodos , Progressão da Doença , Macula Lutea/patologia
16.
Graefes Arch Clin Exp Ophthalmol ; 262(5): 1443-1453, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38197992

RESUMO

PURPOSE: The main purpose of this study was to perform an immunohistochemical, functional, and anatomical evaluation of patients with idiopathic epiretinal membrane (ERM). METHODS: Twenty-four specimens of idiopathic ERM from 24 consecutive patients who underwent 23 G pars plana vitrectomy for ERM and internal limiting membrane (ILM) peeling at the San Juan University Hospital in Alicante (Spain) in 2019 were analyzed. All patients underwent a complete ophthalmological examination including measurement of best corrected visual acuity (BCVA) and macular analysis by spectral-domain optical coherence tomography (SD-OCT) at the time of diagnosis and 3 months after surgery. Specific glial fibrillar acid protein antibodies (GFAP) and S100 calcium-binding protein ß (S100ß) immunostaining markers were used to identify the macroglial component of the ERM, Müller cells, and astrocytes. Ionized calcium-binding adapter molecule 1 protein (Iba1) antibodies were used as specific markers for inflammatory cells, such as microglia and macrophages. RESULTS: Mean preoperative BCVA measured with Snellen chart was 0.3 and 0.6 preoperatively and at 3 months after surgery, respectively. SD-OCT identified 15 patients (62.5%) with a disruption of the outer retinal hyperreflective bands. The immunohistochemical study showed the presence of Müller cells in almost all cases (91.6%), as well of abundant microglia and macrophages. Microglia and macrophages were more frequently present in earlier stages of ERM. Microglia were present in ERM independently of the outer retinal hyperreflective bands integrity as measured by SD-OCT. A greater presence of macrophages was found in those ERMs with no outer retinal hyperreflective band disruption. CONCLUSIONS: Müller cells seem to be the most frequent cell group in ERMs, with also presence of microglia cells and macrophages. Astrocytes were more frequently found in early stages of ERMs. Microglia and macrophages were most frequent in ERMs with early stage (1, 2, or 3) than in advanced stages (4).


Assuntos
Membrana Epirretiniana , Humanos , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Retina , Vitrectomia/métodos , Membrana Basal/cirurgia , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos
17.
BMC Ophthalmol ; 24(1): 293, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026209

RESUMO

OBJECTIVE: This study aimed to evaluate and explore the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling and gas tamponade in treating myopic foveoschisis (MF) through a meta-analysis. METHODS: Systematic searches were conducted on the PubMed, Web of Science and National Library of Medicine (NLM) English-language databases and the China National Knowledge Infrastructure (CNKI) and Wanfang Chinese-language databases. The primary outcome measures were postoperative best-corrected visual acuity (BCVA) and central foveal thickness (CFT), with the secondary outcome being the postoperative complication rate. Data analysis was performed using RevMan5.3 software. RESULTS: A total of 10 studies involving 234 eyes were included. The meta-analysis results showed the following: (1) The average postoperative BCVA improved compared with preoperative levels, with an average improvement in the logarithm of the minimum angle of resolution of 0.40, a statistically significant difference (95% CI: -0.44, - 0.20, p < 0.001); (2) the rate of postoperative BCVA improvement was 77% (95% CI: 65%, 90%, p < 0.001); (3) the postoperative CFT significantly decreased by an average of 385.92 µm, a statistically significant difference (95% CI: -437.85, - 333.98, p < 0.001); (4) the postoperative macular retinal complete reattachment rate was 90% (95% CI: 83%, 97%, p < 0.001); (5) the most common postoperative complication was a cataract, with an incidence of 55.9%. CONCLUSION: Using PPV combined with ILM peeling and gas tamponade to treat MF is reliable.


Assuntos
Membrana Basal , Tamponamento Interno , Retinosquise , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Retinosquise/cirurgia , Tamponamento Interno/métodos , Acuidade Visual/fisiologia , Membrana Basal/cirurgia , Miopia Degenerativa/cirurgia , Miopia Degenerativa/complicações , Miopia Degenerativa/fisiopatologia , Miopia/cirurgia , Miopia/fisiopatologia
18.
BMC Ophthalmol ; 24(1): 333, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123164

RESUMO

PURPOSE: To investigate whether intravitreal antiviral injection (IAI) during vitrectomy reduces the postsurgical retinal detachment (RD) rate and improves the visual prognosis of patients with acute retinal necrosis (ARN). METHODS: This retrospective cohort study included ARN patients treated at a tertiary hospital between January 2013 and December 2020. Patients who underwent pars plana vitrectomy (PPV) alone or combined with intraoperative IAI were classified in PPV-only group and PPV + IAI group, respectively. The incidence of postsurgical RD and the best corrected visual acuity (BCVA) between the groups was compared. A multivariate Cox hazard analysis was employed to explore the risk factors of postsurgical RD. A multivariate logistic regression analysis was applied to assess the impact of intraoperative IAI on preventing severe vision loss (SVL). RESULTS: Fifty-seven eyes with ARN with a median follow-up of 18.5 months were included in the study. There was no significant association between intraoperative IAI during vitrectomy and a reduced risk of postsurgical RD (hazard ratio [HR], 2.65; 95% CI, 0.71-9.89) or SVL at the 6-month follow-up visit (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.25-3.35). Better baseline best-corrected visual acuity (BCVA) was identified to associate with a higher risk of postsurgical RD (HR, 0.33; 95% CI, 0.14-0.81) and a lower risk of SVL at 6 months (OR, 2.28; 95% CI, 1.10-4.89). CONCLUSION: We did not observe a significant effect of intraoperative IAI on the anatomic and visual outcomes of ARN patients in this study. Intraoperative IAI may not be a necessary treatment option for ARN patients who receive vitrectomy.


Assuntos
Antivirais , Injeções Intravítreas , Síndrome de Necrose Retiniana Aguda , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Síndrome de Necrose Retiniana Aguda/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Infecções Oculares Virais/cirurgia , Idoso , Seguimentos , Adulto , Descolamento Retiniano/cirurgia
19.
BMC Ophthalmol ; 24(1): 370, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187836

RESUMO

BACKGROUND: Macular hole (MH) is a rare complication of retinitis pigmentosa (RP) and has an adverse impact on residual visual function. At present, the underlying mechanisms are not fully understood and surgical experience is limited. METHODS: We reviewed the medical records and optical coherence tomography (OCT) scans in a cohort of eight eyes of seven RP patients with MH in order to report their OCT features and vitreoretinal surgical prognosis. RESULTS: This study includes four lamellar macular holes (LMHs) and four full-thickness macular holes (FTMHs). Pre-operative OCT revealed other macular abnormalities in all eyes, such as epiretinal membrane (ERM), cystoid macular edema (CME), lamellar hole-associated epiretinal proliferation (LHEP) and vitreoretinal traction. MH progression and subjective vision worsening were noted in one LMH eye during a seven-month follow-up. All holes closed after vitrectomy with internal limiting membrane (ILM) peeling. At final follow-up, one eye had improved vision and seven eyes remained stable compared to baseline. CONCLUSIONS: The occurrence of MH in RP is accompanied by various imaging characteristics, such as ERM, CME and LHEP, suggesting a multifactorial pathogenesis. Considering poor vision in most RP patients with potentially progressive MH, surgery appears to be effective in maintaining or improving the central vision in a period of time. Thus, vitrectomy should be performed as soon as possible and flap-assisted techniques or episcleral surgeries are needed for some special cases.


Assuntos
Perfurações Retinianas , Retinose Pigmentar , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Tomografia de Coerência Óptica/métodos , Retinose Pigmentar/cirurgia , Retinose Pigmentar/complicações , Retinose Pigmentar/fisiopatologia , Perfurações Retinianas/cirurgia , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Vitrectomia/métodos , Adulto , Idoso , Estudos Retrospectivos , Período Pós-Operatório , Período Pré-Operatório
20.
BMC Ophthalmol ; 24(1): 254, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872161

RESUMO

OBJECTIVE: The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome. METHODS: A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery. RESULTS: This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels. CONCLUSION: RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.


Assuntos
Complicações Pós-Operatórias , Descolamento Retiniano , Síndrome de Necrose Retiniana Aguda , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/etiologia , Síndrome de Necrose Retiniana Aguda/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Acuidade Visual/fisiologia , Complicações Pós-Operatórias/prevenção & controle , Tamponamento Interno , Idoso , Adulto Jovem , Óleos de Silicone/administração & dosagem , Incidência
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