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1.
Eur J Ophthalmol ; : 11206721241245740, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38562036

RESUMO

INTRODUCTION: Deferasirox is the only iron chelator available in oral formulation and a rare cause of pigmentary retinopathy. We report the first case of multimodal imaging in an adult with deferasirox retinopathy. METHODS: Case report and literature review, with search terms including deferasirox retinopathy and deferasirox toxicity. RESULTS: A 63-year-old man with end stage renal disease and transfusion-dependent anemia on deferasirox for one year presented with asymptomatic pigment epitheliopathy. Optical coherence tomography featured outer retinal and retinal pigment epithelial discontinuity corresponding to hypoautofluorescence on fundus autofluorescence and blocking on fluorescein angiography. Multifocal electroretinography revealed subtle reduction in all amplitudes. CONCLUSIONS: Retinal examinations should be considered for patients requiring chronic administration of deferasirox.

3.
PLoS One ; 15(9): e0239138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970724

RESUMO

There are multiple surgical approaches to the repair of rhegmatogenous retinal detachment (RRD). Here, we evaluated the outcomes of small-gauge pars plana vitrectomy (PPV), alone or in combination with scleral buckle (SB-PPV), for RRD repair using a standardized technique by 3 vitreoretinal surgeons: "extensive" removal of the vitreous with scleral depression and dynamic examination of the peripheral retina. One hundred eighty seven eyes of 180 consecutive patients treated for primary RRD by three vitreoretinal surgeons at a tertiary academic medical center from September 2015 to March 2018 were analyzed. Most RRDs occurred in males (134 [71.3%] eyes), affected the left eye (102 [54.3%]), and were phakic (119 [63.3%]). PPV alone was performed in 159 eyes (84.6%), with a combined SB-PPV used in the remaining 29 eyes (15.4%); focal endolaser was used in all (100%) cases. The single surgery anatomic success rate was 186 eyes (99.5%) at 3 months, and 187 (100%) at last follow up. Overall best-corrected visual acuity (BCVA) had significantly improved at 3 months ([Snellen 20/47] P<0.00005) and last follow up ([Snellen 20/31] P<0.00005), as compared to day of presentation ([Snellen 20/234]). Our findings suggest that "extensive" removal of the vitreous and dynamic peripheral examination with scleral depression may lead to high single surgery success in primary uncomplicated RRD repair.


Assuntos
Oftalmopatias Hereditárias/cirurgia , Fotocoagulação a Laser/métodos , Descolamento Retiniano/cirurgia , Recurvamento da Esclera/métodos , Vitrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/métodos , Oftalmopatias Hereditárias/diagnóstico , Feminino , Seguimentos , Humanos , Fotocoagulação a Laser/instrumentação , Masculino , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Retina/cirurgia , Descolamento Retiniano/diagnóstico , Estudos Retrospectivos , Esclera/diagnóstico por imagem , Esclera/cirurgia , Recurvamento da Esclera/instrumentação , Fatores Sexuais , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Vitrectomia/instrumentação
4.
Exp Eye Res ; 198: 108152, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32721424

RESUMO

Over the past century, corneal transplantation has become the most commonly performed allogeneic solid tissue transplantation. Although more than 80% of the corneal transplantations have favorable outcomes, immune-mediated rejection continues to be the major cause of failure in well over 50% of graft recipients that have inflamed and vascularized host beds. Over the past two decades, the progress in our understanding of the immunological pathways that mediate graft rejection has aided in the development of novel therapeutic strategies. In order to successfully test the efficacy of these interventions, it is essential to model the immunological processes occurring as a consequence of corneal transplantation. Herein, we have comprehensively reviewed the established animal models used for replicating the immunopathological processes causing graft rejection in high-risk corneal transplantation settings. We have also discussed the practical and technical differences, as well as biological and immunological variations in different animal models.


Assuntos
Doenças da Córnea/cirurgia , Transplante de Córnea/métodos , Rejeição de Enxerto/prevenção & controle , Animais , Modelos Animais de Doenças
5.
Clin Ophthalmol ; 14: 1759-1767, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616995

RESUMO

OBJECTIVE: To characterize the microvascular retinal changes after repair of macula-off rhegmatogenous retinal detachment (RRD) using optical coherence tomography angiography (OCT-A). PATIENTS AND METHODS: A retrospective review of patients who underwent repair of macula-off RRD. Fellow unaffected eyes were used as controls. Post-operative OCT-A allowed comparison of vessel density (VD) and foveal avascular zone (FAZ) area in the superficial and deep retinal capillary plexus (DCP) as well as VD in the choriocapillaris layer. RESULTS: Seventeen eyes of 17 RRD patients were included in the final analysis. There was a reduction in VD of the deep retinal capillary plexus in affected eyes compared to fellow eyes (p = 0.046). RRD eyes with reduced VD in DCP compared with their fellow control eyes had worse visual acuity after repair compared to those without (p = 0.032). No significant microvasculature changes were detected in the FAZ area and VD in the superficial capillary plexus and choriocapillaris compared to fellow eyes. CONCLUSION: In macula-off RRD eyes, significant microvascular changes were detected in the DCP using OCT-A even after successful anatomical repair. Decreased VD in the DCP compared to the fellow healthy eyes was correlated with worse visual acuity.

6.
Am J Pathol ; 190(9): 1859-1866, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32473919

RESUMO

Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity.


Assuntos
Síndromes do Olho Seco/imunologia , Síndromes do Olho Seco/metabolismo , Receptores da Neurocinina-1/metabolismo , Linfócitos T Reguladores/imunologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
7.
Clin Ophthalmol ; 13: 2093-2096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749606

RESUMO

INTRODUCTION: Significant advances in three-dimensional (3D) imaging technology have allowed for the incorporation of 3D digital displays into medical and surgical devices. Despite initial adoption of the NGENUITY® 3D Visualization System in vitreoretinal surgery, there are limited publications regarding its use. The generally accepted main benefits include improved ergonomics, enhanced surgical team communication and education, reduced retinal phototoxicity, increased depth of field, and display image manipulation. Despite these potential benefits, many retina specialists have questioned its universal applicability to a wide variety of vitreoretinal surgeries. OBJECTIVE: To report on the variety of indications and surgical efficacy of the NGENUITY® 3D Visualization System in vitreoretinal surgery via a review of surgical experience at two vitreoretinal practices in both the academic and community settings. METHODS: A retrospective review was conducted of consecutive surgical cases performed on the NGENUITY® 3D Visualization System at Massachusetts Eye and Ear Infirmary and Florida Retina Institute from June 1st, 2017 to November 1st, 2018. Age, presenting diagnosis, surgical procedure, and intraoperative details were recorded. RESULTS: 272 vitreoretinal surgeries on the Alcon NGENUITY® 3D Visualization System were identified between June 1st, 2017 and November 1st, 2018 at the participating institutions. A detailed breakdown of the indications for surgery and related procedures is reported. During all 272 cases on the 3D digital system, there were no complications attributed to the visualization system. CONCLUSION: This series illustrates the diversity of vitreoretinal surgeries that can be performed on this system without compromising surgical viewing or increasing surgical complications. The Alcon NGENUITY® 3D Visualization System possesses favorable ergonomics, illumination levels, depth of field, display filters, and trainee experience.

8.
Ocul Surf ; 17(3): 393-399, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31009751

RESUMO

Conjunctivochalasis (CCH) is a bilateral conjunctival condition characterized by loose, redundant conjunctival folds, typically in the inferior bulbar conjunctiva. It is a common cause of ocular irritation, especially in older age. For asymptomatic CCH, no treatment is necessary. For treatment of symptomatic CCH, however, a variety of medical and surgical approaches are currently available, which will be thoroughly appraised in this review article. The first step in the management is medical therapy, which involves enhanced lubrication and use of anti-inflammatory medications. In refractory cases, a surgical approach may be undertaken for symptom relief. Several techniques have been described for this, with varying success rates. These include conjunctival cauterization, conjunctival excision, scleral fixation of the conjunctiva, conjunctival ligation, laser conjunctivoplasty, and radiowave electrosurgery. Among these, conjunctival cauterization and excision of the redundant conjunctiva, with or without tissue grafting, have gained popularity.


Assuntos
Anti-Inflamatórios/uso terapêutico , Túnica Conjuntiva/cirurgia , Doenças da Túnica Conjuntiva/terapia , Gerenciamento Clínico , Procedimentos Cirúrgicos Oftalmológicos/métodos , Humanos
9.
Surv Ophthalmol ; 63(4): 554-564, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29128574

RESUMO

Conjunctivochalasis (CCH) is a conjunctival condition characterized by loose, redundant conjunctival folds, most typically in the inferior bulbar conjunctiva of both eyes. Although CCH is a common cause of ocular irritation and discomfort, especially in the elderly, it is often overlooked in clinical practice. CCH may be associated with various ocular and nonocular conditions; however, the most important risk factor is aging. Although often asymptomatic, CCH may cause symptoms related to tear film instability and/or delayed tear clearance. Pathogenesis of CCH remains largely unknown but may involve different elements such as aged conjunctiva, unstable tear film, mechanical friction, ocular surface inflammation, and delayed tear clearance. Contradictory results have been reported on histopathologic changes in CCH, with some studies showing a normal microscopic structure. For symptomatic CCH, medical treatment may include lubrication and anti-inflammatory medications. For symptomatic patients who fail to respond to medical treatment, a surgical procedure may be considered. Although various surgical procedures have been used for CCH, more often, it consists of conjunctival cauterization or excision of the redundant conjunctiva, with or without amniotic membrane transplantation.


Assuntos
Envelhecimento/fisiologia , Doenças da Túnica Conjuntiva , Lágrimas/fisiologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Doenças da Túnica Conjuntiva/etiologia , Doenças da Túnica Conjuntiva/patologia , Doenças da Túnica Conjuntiva/terapia , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/patologia , Humanos , Lubrificantes Oftálmicos/uso terapêutico , Procedimentos Cirúrgicos Oftalmológicos/métodos , Fatores de Risco
10.
Oncotarget ; 8(39): 65778-65788, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029471

RESUMO

PURPOSE: The purpose of this study was to determine the protective effects of Resveratrol (RESV) on acute bright light-induced retinal degeneration in aged senescence accelerated mouse strain. METHODS: Ten three-month-old male SAMP8 mice (prone to aging) were randomly assigned to two experimental dietary groups: one untreated group and one RESV treatment group (n=20 eyes for each group). After 30 days of treatment, mice were exposed to intense bright light. Ten male SAMR1 mice (resistant to aging) served as control (n=20 eyes). The protective effects of RESV administration on light-induced retinal degeneration in SAMP8 strain as well as the effect of bright light damage in the retinas of SAMP8 mice were analyzed by electroretinography (ERG), retinal histology, mRNA, protein and lipid profile. RESULTS: 68%-85% of a-wave amplitude and 72%-92% of b-wave amplitude were persevered by RESV in SAMP8 mice that were exposed to light damage. Also, RESV preserved their photoreceptor nuclei. mRNA expression of neuroprotective factors leukemia inhibitory factor (LIF), brain derived neurotrophic factor (BDNF), oncostatin M (OSM), cardiotrophin 1(CT-1) and cardiotrophin-like cytokine (CLC) were up-regulated 28, 8, 7, 5 and 9-fold in SAMP8 mice after RESV treatment. In addition, RESV could suppress the NF-κB pathway by down-regulating the expression of pIκB. Light damage led to increase of saturated FA, monoenoic FA, n6 PUFA and n6/n3 ratio and decrease of Docosahexaenoic acid (DHA). There was no significant difference on DHA and the ratio of n6/n3-FA between the untreated and RESV treated SAMP8 mice. CONCLUSIONS: Collectively, our study provides evidence that RESV prevents light-induced retinal damage associated with aging.

11.
Invest Ophthalmol Vis Sci ; 58(6): BIO168-BIO173, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28693042

RESUMO

Purpose: To evaluate interobserver concordance in measured corneal fluorescein staining (CFS) using the National Eye Institute/Industry (NEI) grading scale and the Corneal Fluorescein Staining Index (CFSi), a computer-assisted, objective, centesimal scoring system. Methods: We conducted a study to evaluate CFS in clinical photographs of patients with corneal epitheliopathy. One group of clinicians graded CFS in the images using the NEI while a second group applied the CFSi. We evaluated the level of interobserver agreement and differences among CFS scores with each method, level of correlation between the two methods, and distribution of cases based on the CFS severity assigned by each method. Results: The level of interobserver agreement was 0.65 (P < 0.001) with the NEI, and 0.99 (P < 0.001) with the CFSi. There were statistically significant differences among clinicians' measurements obtained with the NEI (P < 0.001), but not with the CFSi (P = 0.78). There was a statistically significant correlation between the CFS scores obtained with the two methods (R = 0.72; P < 0.001). The NEI scale allocated the majority of cases (65%) within the higher quartile in the scale's severity (12-15/15). In contrast, the CFSi allocated the majority of cases (61%) within the lower quartile in the scale's severity (0-25/100). Conclusions: The CFSi is easy to implement, provides higher interobserver consistency, and due to its continuous score can discriminate smaller differences in CFS. Reproducibility of the computer-based system is higher and, interestingly, the system allocates cases of epitheliopathy in different severity categories than clinicians do. The CFSi can be an alternative for objective CFS evaluation in the clinic and in clinical trials.


Assuntos
Doenças da Córnea/diagnóstico por imagem , Técnicas de Diagnóstico Oftalmológico , Fluoresceína , Corantes Fluorescentes , Análise de Variância , Síndromes do Olho Seco/diagnóstico por imagem , Epitélio Corneano/patologia , Humanos , Processamento de Imagem Assistida por Computador , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes
12.
Ocul Surf ; 15(4): 652-659, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28576753

RESUMO

Regulatory T cells (Tregs) are critical modulators of immune homeostasis. Tregs maintain peripheral tolerance to self-antigens, thereby preventing autoimmune disease. Furthermore, Tregs suppress excessive immune responses deleterious to the host. Recent research has deepened our understanding of how Tregs function at the ocular surface. This manuscript describes the classification, the immunosuppressive mechanisms, and the phenotypic plasticity of Tregs. We review the contribution of Tregs to ocular surface autoimmune disease, as well as the function of Tregs in allergy and infection at the ocular surface. Finally, we review the role of Tregs in promoting allotolerance in corneal transplantation.


Assuntos
Linfócitos T Reguladores , Olho , Humanos , Imunossupressores
13.
Medicine (Baltimore) ; 95(30): e4350, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27472722

RESUMO

To compare the surgical duration and clinical outcomes of nasolacrimal recanalization versus external dacryocystorhinostomy (DCR) in the treatment of failed nasolacrimal duct intubation.This is a retrospective, comparative, and interventional study. We evaluated the outcomes of 66 consecutive patients undergoing either nasolacrimal recanalization (n = 32) or DCR (n = 34) in a tertiary lacrimal disease referral center. Length of surgical duration, clinical outcomes, and rate of recurrence at 18 months postoperatively were compared.The mean surgical duration was 18.5 minutes (range, 15-25 minutes) for nasolacrimal recanalization and 48.2 minutes (range, 45-61 minutes) for DCR, respectively (P < 0.001). The rate of success was 84.4% in the recanalization group and 85.3% in the DCR group, respectively (P = 0.91). The time to recurrence was 2.6 ±â€Š1.1 months in the recanalization group and 5.6 ±â€Š2.1 months in the DCR group (P < 0.001). Five failed cases in each group received a secondary DCR surgery with the same resolution rate (40%). The absence of ocular discharge at baseline was a significant predictor for a successful outcome in the recanalization group (P = 0.04) but not in the DCR group (P = 0.63).Nasolacrimal recanalization is an effective, safe, and time-saving alternative to DCR for the treatment of failed nasolacrimal duct intubation. Clinicians should be cautious in patients with discharge.


Assuntos
Dacriocistorinostomia , Intubação , Ducto Nasolacrimal/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Recidiva , Reoperação , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento
14.
Cell Mol Life Sci ; 73(22): 4249-4264, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27314883

RESUMO

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.


Assuntos
Imunidade , Substância P/metabolismo , Sequência de Aminoácidos , Animais , Doença , Humanos , Imunomodulação , Transdução de Sinais , Substância P/química
15.
Cornea ; 35(3): 363-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26606299

RESUMO

PURPOSE: To evaluate the effect of frame size on the calculated corneal endothelial cell density (CECD) in images of laser scanning in vivo confocal microscopy (IVCM). METHODS: Forty-nine corneal endothelial images acquired by laser scanning IVCM (Heidelberg Retina Tomograph 3 with Rostock Corneal Module) with different endothelial cell densities were analyzed. In each image (160,000 µm), the CECD was calculated using the fixed-frame method by counting cells in the following frame sizes: 80,000 µm, 40,000 µm, 20,000 µm, 10,000 µm, 5000 µm, and 2500 µm. The calculated CECD was then compared with that of the variable-frame method as the reference value. RESULTS: There was no significant difference in the calculated CECD between the variable-frame method (2004 ± 832 cells/mm), and the fixed-frame method using a 40,000-µm frame (2023 ± 810 cells/mm). On the other hand, the calculated CECD showed significant overestimations in frame sizes of 20,000 µm (2066 ± 820 cells/mm), 10,000 µm (2156 ± 785 cells/mm), 5000 µm (2352 ± 783 cells/mm), and 2500 µm (2715 ± 754 cells/mm), with P < 0.001 in all. This resulted in overestimations of 4.8 ± 9.8%, 11.9 ± 16.2%, 24.9 ± 23.1%, and 49.1 ± 38.8% for these frame sizes, respectively. Images with lower CECD demonstrated higher overestimations of cell density in smaller frame sizes. CONCLUSIONS: In laser scanning IVCM images, there is significant overestimation of CECD if the cells are counted in frames smaller than 25% of the image. Similar frame sizes should be used when monitoring CECD over time.


Assuntos
Células Endoteliais/citologia , Endotélio Corneano/citologia , Microscopia Confocal , Contagem de Células/métodos , Humanos , Valores de Referência
16.
Exp Eye Res ; 124: 67-73, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24837142

RESUMO

Verteporfin (VP), a benzoporphyrin derivative, is clinically used in photodynamic therapy for neovascular macular degeneration. Recent studies indicate that VP may inhibit growth of hepatoma cells without photoactivation through inhibition of YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human retinoblastoma cell lines. Verteporfin but not vehicle control inhibited the growth, proliferation and viability of human retinoblastoma cell lines (Y79 and WERI) in a dose-dependent manner and was associated with downregulation of YAP-TEAD associated downstream proto-oncogenes such as c-myc, Axl, and surviving. In addition VP affected signals involved in cell migration and angiogenesis such as CTGF, cyr61, and VEGF-A but was not associated with significant effect on the mTOR/autophagy pathway. Of interest the pluripotency marker Oct4 were downregulated by Verteporfin treatment. Our results indicate that the clinically used photosensitizer VP is a potent inhibitor of cell growth in retinoblastoma cells, disrupting YAP-TEAD signaling and pluripotential marker OCT4. This study highlights for the first time the role of the YAP-TEAD pathway in Retinoblastoma and suggests that VP may be a useful adjuvant therapeutic tool in treating Rb patients.


Assuntos
Fotoquimioterapia/métodos , Porfirinas/uso terapêutico , Retina/patologia , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Pré-Escolar , Relação Dose-Resposta a Droga , Seguimentos , Humanos , Lactente , Recém-Nascido , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/administração & dosagem , Retina/efeitos dos fármacos , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Células Tumorais Cultivadas , Verteporfina
17.
Invest Ophthalmol Vis Sci ; 55(7): 4175-85, 2014 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-24781943

RESUMO

PURPOSE: To evaluate the effects and mechanism of aminoimidazole carboxamide ribonucleotide (AICAR), an AMP-dependent kinase (AMPK) activator, on the growth of uveal melanoma cell lines. METHODS: Four different cell lines were treated with AICAR (1-4 mM). Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Cell cycle analysis was conducted by flow cytometry; additionally, expression of cell-cycle control proteins, cell growth transcription factors, and downstream effectors of AMPK were determined by RT-PCR and Western blot. RESULTS: Aminoimidazole carboxamide ribonucleotide inhibited cell growth, induced S-phase arrest, and led to AMPK activation. Aminoimidazole carboxamide ribonucleotide treatment was associated with inhibition of eukaryotic translation initiation factor 4E-BP1 phosphorylation, a marker of mammalian target of rapamycin (mTOR) pathway activity. Aminoimidazole carboxamide ribonucleotide treatment was also associated with downregulation of cyclins A and D, but had minimal effects on the phosphorylation of ribosomal protein S6 or levels of the macroautophagy marker LC3B. The effects of AICAR were abolished by treatment with dipyridamole, an adenosine transporter inhibitor that blocks the entry of AICAR into cells. Treatment with adenosine kinase inhibitor 5-iodotubericidin, which inhibits the conversion of AICAR to its 5'-phosphorylated ribotide 5-aminoimidazole-4-carboxamide-1-D-ribofuranosyl-5'-monophosphate (ZMP; the direct activator of AMPK), reversed most of the growth-inhibitory effects, indicating that some of AICAR's antiproliferative effects are mediated at least partially through AMPK activation. CONCLUSIONS: Aminoimidazole carboxamide ribonucleotide inhibited uveal melanoma cell proliferation partially through activation of the AMPK pathway and downregulation of cyclins A1 and D1.


Assuntos
Aminoimidazol Carboxamida/análogos & derivados , Ativação Enzimática/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , RNA Neoplásico/genética , Ribonucleotídeos/farmacologia , Serina-Treonina Quinases TOR/genética , Neoplasias Uveais/genética , Aminoimidazol Carboxamida/farmacologia , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Humanos , Melanoma/tratamento farmacológico , Melanoma/enzimologia , Fosfotransferases (Aceptor do Grupo Fosfato)/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/enzimologia
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