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1.
Mol Med ; 30(1): 109, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060957

RESUMO

Primary cilia are sensory organelles that extend from the cellular membrane and are found in a wide range of cell types. Cilia possess a plethora of vital components that enable the detection and transmission of several signaling pathways, including Wnt and Shh. In turn, the regulation of ciliogenesis and cilium length is influenced by various factors, including autophagy, organization of the actin cytoskeleton, and signaling inside the cilium. Irregularities in the development, maintenance, and function of this cellular component lead to a range of clinical manifestations known as ciliopathies. The majority of people with ciliopathies have a high prevalence of retinal degeneration. The most common theory is that retinal degeneration is primarily caused by functional and developmental problems within retinal photoreceptors. The contribution of other ciliated retinal cell types to retinal degeneration has not been explored to date. In this review, we examine the occurrence of primary cilia in various retinal cell types and their significance in pathology. Additionally, we explore potential therapeutic approaches targeting ciliopathies. By engaging in this endeavor, we present new ideas that elucidate innovative concepts for the future investigation and treatment of retinal ciliopathies.


Assuntos
Cílios , Ciliopatias , Doenças Neurodegenerativas , Retina , Cílios/metabolismo , Cílios/patologia , Humanos , Ciliopatias/genética , Ciliopatias/metabolismo , Ciliopatias/patologia , Animais , Retina/metabolismo , Retina/patologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/patologia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/etiologia , Transdução de Sinais
2.
Int J Mol Sci ; 25(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38791518

RESUMO

Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-ß) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-ß-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.


Assuntos
Neovascularização da Córnea , Humanos , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/terapia , Neovascularização da Córnea/metabolismo , Animais , Terapia Genética/métodos , Inibidores da Angiogênese/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo
3.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474172

RESUMO

Aland island eye disease (AIED), an incomplete form of X-linked congenital stationary night blindness (CSNB2A), and X-linked cone-rod dystrophy type 3 (CORDX3) display many overlapping clinical findings. They result from mutations in the CACNA1F gene encoding the α1F subunit of the Cav1.4 channel, which plays a key role in neurotransmission from rod and cone photoreceptors to bipolar cells. Case report: A 57-year-old Caucasian man who had suffered since his early childhood from nystagmus, nyctalopia, low visual acuity and high myopia in both eyes (OU) presented to expand the diagnostic process, because similar symptoms had occurred in his 2-month-old grandson. Additionally, the patient was diagnosed with protanomalous color vision deficiency, diffuse thinning, and moderate hypopigmentation of the retina. Optical coherence tomography of the macula revealed retinoschisis in the right eye and foveal hypoplasia in the left eye. Dark-adapted (DA) 3.0 flash full-field electroretinography (ffERG) amplitudes of a-waves were attenuated, and the amplitudes of b-waves were abolished, which resulted in a negative pattern of the ERG. Moreover, the light-adapted 3.0 and 3.0 flicker ffERG as well as the DA 0.01 ffERG were consistent with severely reduced responses OU. Genetic testing revealed a hemizygous form of a stop-gained mutation (c.4051C>T) in exon 35 of the CACNA1F gene. This pathogenic variant has so far been described in combination with a phenotype corresponding to CSNB2A and CORDX3. This report contributes to expanding the knowledge of the clinical spectrum of CACNA1F-related disease. Wide variability and the overlapping clinical manifestations observed within AIED and its allelic disorders may not be explained solely by the consequences of different mutations on proteins. The lack of distinct genotype-phenotype correlations indicates the presence of additional, not yet identified, disease-modifying factors.


Assuntos
Albinismo Ocular , Oftalmopatias Hereditárias , Doenças Genéticas Ligadas ao Cromossomo X , Miopia , Cegueira Noturna , Doenças Retinianas , Retinose Pigmentar , Retinosquise , Masculino , Humanos , Pré-Escolar , Lactente , Pessoa de Meia-Idade , Canais de Cálcio Tipo L/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Retina/metabolismo , Mutação
4.
Medicina (Kaunas) ; 59(2)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36837600

RESUMO

Background: Cone-rod dystrophies (CRDs) are a heterogeneous group of inherited retinal diseases (IRDs) characterized by cone photoreceptor loss, that is followed by subsequent rod photoreceptor impairment. Case presentation: A 49-year-old man complaining of diminution of vision in both eyes (OU) was referred to our outpatient clinic. He reported visual loss for 5 years, but it was most progressive during the last few months. The best-corrected visual acuity (BCVA) at presentation was 0.4 in the right eye (RE) and 1.0 in the left eye (LE). Fundus fluorescein angiography (FFA) revealed granular hyperfluorescence in the macula and concomitant areas of capillary atrophy. Flash full-field electroretinography (ffERG) showed lowering of a and b waves as well as prolonged peak time in light-adapted conditions. However, outcomes of dark-adapted ERGs were within normal limits. Based on the constellation of clinical, angiographic, and electrophysiological tests findings, a diagnosis of IRD was suspected. Genetic testing showed a homozygous, pathogenic c.783G>A mutation in the cadherin-related family member 1 (CDHR1) gene, which confirmed CRD type 15 (CRD15). Conclusions: We demonstrate the clinical characteristics, retinal imaging outcomes, and genetic test results of a patient with CRD15. Our case contributes to expanding our knowledge of the clinical involvement of the pathogenic mutation c.783G>A in CDHR1 variants.


Assuntos
Distrofias de Cones e Bastonetes , Masculino , Humanos , Pessoa de Meia-Idade , Distrofias de Cones e Bastonetes/genética , Distrofias de Cones e Bastonetes/patologia , Tomografia de Coerência Óptica , Retina , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Mutação , Testes Genéticos , Proteínas Relacionadas a Caderinas , Proteínas do Tecido Nervoso/genética
5.
J Clin Med ; 13(14)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39064267

RESUMO

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have been identified, which can be divided into non-modifiable, including genetic factors, age, and sex, and modifiable or environmental factors, such as smoking, poor diet, and hypertension. Early stages of age-related macular degeneration are characterized by fundus drusen and abnormalities in the retinal pigment epithelium. In late stages, geographic atrophy and choroidal neovascularization (CNV) are observed. The treatment of AMD, especially its advanced forms, is very challenging. Intensive research has made it possible to treat advanced stages of the dry form of AMD with pegcetacoplan and avacincaptad pegol, new drugs approved for use in the US. Pegcetacoplan targets the C3 and avacincaptad pegol targets the C5, the pivotal proteins of the complement cascade. The drugs are administered by intravitreal injection. The gold standard for neovascular AMD (nAMD) consists of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. Treatment can be administered according to the fixed, pro-re-nata, and treat-and-extend regimens. The latter seems to have the best effect on improving visual acuity (VA) and the maximum therapeutic benefit. The search continues for the best ways to deliver intravitreal drugs. Current methods include sustained-release implants and hydrogel platforms for drug release, while the most promising future pathways for treating dry and nAMD are stem cell and gene therapy.

6.
Exp Eye Res ; 106: 14-23, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23089144

RESUMO

Age-related macular degeneration (AMD) is a degenerative disease of the eye, triggered by the damage of the macular cells. In the Western world it is the most frequent cause of blindness in the elderly. Oxidative stress is proved to play a key role in AMD pathogenesis and since iron accumulation has been found in AMD maculas, it may accelerate the oxidative processes in this tissue. In the present work we investigated the association between four polymorphisms of the transferrin gene (rs8177178; rs8177179; rs4481157; rs1130459) and AMD in dependence on the transferrin protein and iron serum levels. We employed PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) for genotype determination, ELISA assay for serum transferrin evaluation and colorimetric assay for measurement of iron concentration in the serum. We found that advanced age and AMD family history may be independent risk factors for AMD (1.02, p < 0.05 and 8.88, p < 0.001, respectively). At the rs4481157 site The GG genotype of the rs4481157 polymorphism decreased the risk of dry AMD (OR 0.50; p < 0.05), while the GA increased this risk (OR 1.07; p < 0.05). Moreover, the GA genotype of this polymorphism decreased the risk of progression to the wet form (OR 0.63; p < 0.05). The analysis of the gene-environment interactions showed that the rs4481157 polymorphism modulates the AMD risk among obese (BMI above 30) individuals. In the former smokers group we observed a moderate association between rs4481157 polymorphism and AMD risk while this association in current smokers was stronger. We found also that the serum level of transferrin was higher in the AMD group (p < 0.001) than in the control, but the total serum iron levels did not differ between both groups. We found that the serum transferrin was associated with the rs8177178 (p < 0.001) and rs4481157 (p < 0.01) polymorphisms, and the common variant (GG) of both sites was related to a lower level of transferrin. Presented data may contribute to the involvement of iron homeostasis in AMD risk.


Assuntos
Degeneração Macular/sangue , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Transferrina/genética , Idoso , Corantes , Ensaio de Imunoadsorção Enzimática , Feminino , Angiofluoresceinografia , Interação Gene-Ambiente , Genótipo , Homeostase , Humanos , Verde de Indocianina , Compostos de Ferro/sangue , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Tomografia de Coerência Óptica , Transferrina/metabolismo
7.
Life (Basel) ; 14(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38276263

RESUMO

PURPOSE: To examine the effectiveness of a standardized combination of intracameral mydriatics and anesthetic (SCIMA) on mydriasis in patients with coexisting diseases such as diabetes mellitus (DM) and pseudoexfoliation syndrome (PXF) during phacoemulsification. METHODS: Patients with cataract were included in the study if they achieved pupil dilation diameter ≥ 6.0 mm after the administration of mydriatic eyedrops (ME) during the first visit (V1). During the second visit (V2), pupil size measurements were obtained for phacoemulsification surgery with SCIMA. Effective mydriasis was defined as a pupil diameter ≥ 6.0 mm just prior to capsulorhexis without the use of additional pupil dilating agents. The measurements after ME administration during V1 and after SCIMA use during V2 were compared. RESULTS: 103 patients (103 eyes) were divided into 3 groups: cataract and DM (n = 35), cataract and PXF (n = 32), and cataract without DM or PXF (n = 36). SCIMA administration allowed the achievement of effective mydriasis (≥6.0 mm) in all groups (n = 103; 100%). Mydriasis was significantly larger (p ≤ 0.001) after ME (7.3 mm) than after SCIMA (6.8 mm) administration. CONCLUSIONS: Patients with cataract and such comorbidities as DM or PXF are likely to achieve effective pharmacological mydriasis during cataract phacoemulsification after SCIMA application. Mydriasis after ME is slower and larger, while SCIMA is faster.

8.
Mol Biol Rep ; 39(3): 2081-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21647550

RESUMO

Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber-Weiss or Fenton reaction. On the other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the -42 + 1444 position in the HMOX2 gene (the -42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the -42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the -42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the -42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the -42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD.


Assuntos
Predisposição Genética para Doença/genética , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase-1/genética , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Associação Genética , Genótipo , Humanos , Modelos Logísticos , Degeneração Macular/fisiopatologia , Razão de Chances , Polônia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
9.
Med Sci Monit ; 18(1): PI1-4, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22207126

RESUMO

BACKGROUND: The expectations of post-removal cataract surgery patients are extremely high, and best vision acuity is expected. The best refractive results are influenced by two factors - cataract surgical removal and the corneal astigmatism correction. Currently, the two most often applied corneal astigmatism removal methods are laser surgery and toric intraocular lens implantation, with the latter method being both more stable and more reversible. This study aimed to estimate the surgical astigmatism correction efficiency after AcrySof Toric intraocular lens implantation in patients with corneal astigmatism. MATERIAL/METHODS: We used the AcrySof Toric IOL 1-part hydrophobic acrylic lenses. The retrospective research covered 30 eyeballs in 28 cataract and corneal astigmatism patients, with the AcrySof Toric lens implanted by one surgeon. RESULTS: In our test group 92.31% of post-surgical patients (phacoemulsification and toric lenses implantation) gained the best uncorrected visual acuity, range 0.6-1.0; and in 7.69% of patients the acuity was 0.4-0.6. Lens rotation was examined three weeks after the surgical procedure and a 3.24 ± 3.41 degree axial displacement was observed; however, this lens rotation was clinically unimportant. Based on the analysis of post-surgical results, the corneal astigmatism was 84.2% lower than before the procedure. CONCLUSIONS: We noticed clinically and statistically important vision acuity improvement in the corneal astigmatism patients. The patients' high satisfaction was conditioned by proper pre-surgery qualification. Astigmatism correction by cataract removal surgery is a safe and effective surgical solution. In the future, we expect the use of toric intraocular lenses will become widespread and significant.


Assuntos
Astigmatismo/cirurgia , Implante de Lente Intraocular/métodos , Lentes Intraoculares , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual/fisiologia
10.
Graefes Arch Clin Exp Ophthalmol ; 250(7): 1057-65, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22371024

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is an ocular disease affecting macula - the central part of the retina, resulting in the degeneration of photoreceptors and retinal epithelium and causing severe central vision impairment. The pathophysiology of the disease is not completely known, but a significant role is attributed to genetic factors. The contribution of oxidative stress in AMD as a trigger of the degenerative process is well-established. Iron ions may act as a source of reactive oxygen species; therefore, maintaining iron homeostasis is important for redox balance in the organism. Diversity in iron homeostasis genes may counterpart in unbalanced redox state, and thus be involved in AMD pathophysiology. METHODS: In this work, we searched for an association between some single nucleotide polymorphisms in the divalent metal transporter 1 (DMT1) gene intronic IVS4+44C>A (rs224589) and 3'-UTR c.2044T>C (rs2285230) and environmental factors and AMD. Genotyping was performed using the PCR-RFLP method. DNA was obtained from 436 AMD patients and 168 controls. RESULTS: We did not find any association between the genotypes of the two polymorphisms and AMD occurrence. However, we observed that AMD patients living in a rural environment and having the CC genotype of the IVS4+44C>A polymorphism had an increased risk of AMD, while individuals with the CA genotype or the A allele had a decreased risk of the disease. Moreover, in male AMD patients the C allele increased the risk of the disease, while the AA genotype decreased it. CONCLUSIONS: These results suggest that the VS4+44C>A polymorphism of the DMT1 gene may interact with place of living and gender to modulate the risk of AMD.


Assuntos
Proteínas de Transporte de Cátions/genética , Atrofia Geográfica/genética , Polimorfismo de Nucleotídeo Único , Degeneração Macular Exsudativa/genética , Feminino , Angiofluoresceinografia , Interação Gene-Ambiente , Genótipo , Atrofia Geográfica/diagnóstico , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , População Rural , Inquéritos e Questionários , Tomografia de Coerência Óptica , População Urbana , Degeneração Macular Exsudativa/diagnóstico
11.
Med Sci Monit ; 18(2): CR51-57, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22293877

RESUMO

BACKGROUND: Central serous chorioretinopathy (CSC) is a condition that originates from alterations of the choroidal circulation. The aim of this paper was to evaluate the use of indocyanine green angiography (ICGA) in patients with chronic CSC. MATERIAL/METHODS: The analysis included 17 patients (34 eyes) with chronic CSC in at least 1 eye. The eye examination included: distance and near visual acuity, biomicroscopy, applanation tonometry, fundus examination, colored and red-free fundus photography, evaluation of autofluorescence, optical coherence tomography, and fluorescein and indocyanine green angiography. RESULTS: In 34 eyes (100%) involved in the ICGA study the results revealed zones of transient increased choroidal vessels permeability. In 18 eyes (52.9%) choroidal changes were accompanied by a focal serous pigment epithelial detachment. In 4 eyes (11.8%) of 3 patients' the ICGA examination confirmed the presence of occult choroidal neovascularization (CNV). In the patient with bilateral diffuse retinal pigment epitheliopathy, CNV was present in 1 eye, in the patient with unilateral chronic CSC it was also present in 1 eye, and in the third patient with bilateral chronic CSC it was detected in both eyes. CONCLUSIONS: ICGA is a very useful examination that enables ophthalmologists to visualize choroidal changes due to chronic CSC, as well as to diagnose occult CNV in chronic CSC.


Assuntos
Angiografia , Coriorretinopatia Serosa Central/diagnóstico , Verde de Indocianina , Idoso , Coriorretinopatia Serosa Central/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Tonometria Ocular , Acuidade Visual
12.
Med Sci Monit ; 17(5): CS60-2, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21525817

RESUMO

BACKGROUND: The aim of this study was to report on epithelial posttraumatic iris cyst that was successfully treated with needle aspiration and surgical excision with surrounding iris tissue. CASE REPORT: A 30-year-old women was treated for a large fluid-filled cyst in the anterior chamber of the left eye; 25 years before, she had an open globe injury. She observed deterioration of her visual acuity 1 year before her visit to our clinic. During ophthalmological examination, an iris cyst was diagnosed. As a result, she had Nd: YAG laser puncture of the cyst in the left eye, performed 5 months before she came to our clinic. After a short time of decompression, the cyst rapidly grew in size (2/3 of the anterior chamber), and her visual acuity was getting worse due to an aggressive growth of the iris cyst. Visual acuity was 0.06. Needle aspiration with surgical excision of the cyst with surrounding iris tissue was performed. Histopathologic examination confirmed an epithelial cyst. At the 1-year follow-up, there was no evidence of recurrence of the iris cyst, and BCVA was 0.2. CONCLUSIONS: This case report provides evidence that needle aspiration with surgical excision of iris cyst seems to be an effective treatment method of this complication.


Assuntos
Cistos/cirurgia , Epitélio/patologia , Doenças da Íris/patologia , Doenças da Íris/cirurgia , Iris/patologia , Iris/cirurgia , Ferimentos e Lesões/complicações , Adulto , Biópsia por Agulha Fina , Pré-Escolar , Cistos/etiologia , Cistos/patologia , Epitélio/cirurgia , Feminino , Humanos , Ferimentos e Lesões/cirurgia
13.
Med Sci Monit ; 17(6): CS70-4, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21629193

RESUMO

BACKGROUND: Perioperative optic neuropathy is a disease which can lead to serious, irreversible damage of vision. This complication could be the result of non-ocular surgery, for example, cardiac or spinal procedures. We present a case of anterior ischemic neuropathy (AION) which occurred following a conventional coronary artery bypass graft procedure. CASE REPORT: A 57-year-old man, 4 days after Conventional Coronary Artery Bypass Graft surgery as result of multi-vessel stabile coronary artery disease and history of anterolateral wall myocardial infarction, was admitted to the Eye Clinic due to significant loss of vision in his right eye. The patient had hypertension and was a heavy smoker. On admission, the slit lamp examination revealed a relative afferent pupillary defect in the right eye. The fundus examination showed optic disc edema with the presence of flame hemorrhages. Best corrected visual acuity (BCVA) was 0.02. The results of eye examination and fluorescein angiography confirmed the diagnosis of AION. Anti-aggregation and antithrombotic treatment was continued with steroids and vasodilators. After 7 days of this treatment we noticed the improvement of BCVA to 0.2. At 6-month follow-up, the vision was stable, and fundus examination revealed optic disc atrophy. CONCLUSIONS: After cardiac surgical operations, such as coronary artery bypass graft procedures, anterior ischemic optic neuropathy may occur. In those cases, close cooperation between the various specialists is necessary.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Neuropatia Óptica Isquêmica/etiologia , Olho/irrigação sanguínea , Olho/diagnóstico por imagem , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/diagnóstico por imagem , Radiografia
14.
Tohoku J Exp Med ; 223(4): 253-61, 2011 04.
Artigo em Inglês | MEDLINE | ID: mdl-21422745

RESUMO

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries, and its pathogenesis is underlined by genetic and environmental factors. Oxidative stress is a major environmental risk factor of AMD; namely, AMD is associated with the increased level of reactive oxygen species, which may be produced in reactions catalyzed by iron present in the retina. Therefore, variability of the genes of iron metabolism may be important in the AMD risk. In the present study, we analyzed the association between AMD and the -576G>A polymorphism of the transferrin gene or the 1892C>T polymorphism of the transferrin receptor 2 (TFR2) gene in 278 patients with AMD and 105 controls. The former polymorphism is located in the promoter region of the transferrin gene and may affect the level of its transcription, while the latter is a synonymous mutation in the exon 16, which may affect the efficiency of translation of TFR2 mRNA. Transferrin and TFR2 are important in iron homeostasis. The A allele of the -576A>G polymorphism was significantly associated with the increased risk of AMD in tobacco smokers, whereas the 1892C>T polymorphism did not influence the risk of AMD related to smoking. Moreover, each polymorphism does not influence the risk of AMD associated with age, sex or the family history of the disease. In conclusion, the A allele of the -576A>G polymorphism of the transferrin gene may increase the risk of AMD in smokers.


Assuntos
Alelos , Degeneração Macular/genética , Polimorfismo de Nucleotídeo Único , Fumar , Transferrina/genética , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Degeneração Macular/complicações , Degeneração Macular/epidemiologia , Masculino , Polimorfismo de Nucleotídeo Único/fisiologia , Risco , Fumar/epidemiologia , Fumar/genética
15.
Pharmacol Rep ; 71(1): 175-182, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30554037

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes and the leading cause of acquired blindness in adults. In diabetic patients hyperglycemia induces complex metabolic abnormalities affecting retinal homeostasis, and promotes retinal inflammation and angiogenesis. Incretin mimetic drugs such exenatide, are a relatively new group of drugs used in the treatment of diabetes. We investigated the potential direct effects of exenatide on human retinal pigment epithelium (HRPE). METHODS: cAMP production was measured after stimulation of HRPE cells with GLP-1 and exenatide. Intracellular signaling pathways were also examined. HRPE cells were stimulated with TNF-α and subsequently incubated with exenatide. The concentration of metalloproteinases, MMP-1, MMP-2 and MMP-9, and tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and TIMP-3 were evaluated. Viability, cytotoxicity and caspase 3/7 activation were determined. Activity of dipeptidyl peptidase-4 (DPP-4), an enzyme involved in GLP-1 inactivation, was also determined. RESULTS: Both GLP-1 and exenatide stimulation in HRPE cells caused no effect in cAMP levels suggesting alternative signaling pathways. Signaling pathway analysis showed that exenatide reduced phosphorylation of Akt-Ser473, PRAS40, SAPK/JNK, Bad, and S6 proteins but not Akt-Thr308. Exenatide also decreased MMP-1, MMP-9, and TIMP-2 protein levels whereas MMP-2 level in HRPE cells was increased. Finally, we show that exenatide decreased the activity of DPP-4 in TNF-α stimulated HRPE cells. CONCLUSIONS: These findings indicate that exenatide modulates regulation of extracellular matrix components involved in retinal remodeling.


Assuntos
Colagenases/metabolismo , Células Epiteliais/efeitos dos fármacos , Exenatida/farmacologia , Hipoglicemiantes/farmacologia , Incretinas/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Inibidores Teciduais de Metaloproteinases/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Linhagem Celular , Células Epiteliais/enzimologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/enzimologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Epitélio Pigmentado da Retina/enzimologia , Transdução de Sinais/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo
16.
Clin Hemorheol Microcirc ; 38(3): 209-16, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18239263

RESUMO

The aim of this study was to correlate some pathogenetic factor with the hemorheological parameters in ills with age-related macular degeneration. The studies were performed on 52 patients suffering from AMD. The control group consisted of 42 healthy persons. Blood samples were taken from patients immediately after ophthalmological examination from antecubital vein and anticoagulated with K3EDTA. The symptoms of macular degeneration were drusen; changes in retinal pigmentation, areolar atrophy, neovascularization. Blood viscosity measurements were performed with use of cone-plate Brookfield viscometer at sheer rate 150 s(-1) and plasma viscosity with capillary Ubbelohde's viscometer. Fibrinogen concentration has been measured according to Clauss method, and level of triglycerides was measured using coupled enzymatic reactions. Haematocrit level was measured with the help of micromethod. The viscosity of whole blood, corrected viscosity and plasma viscosity were respectively 6.9%, 14.6% and 15.7% higher in the patient group than in the control group, while fibrinogen-plasma factor was 16% higher. Aggregation amplitude and time t(1/2) were 89.3% and 28.6% lower in AMD group. Erythrocyte deformability was 18% lower. The aggregation index was 7.6% higher in the AMD group then in the control group. Summing up in people suffering from AMD rheological disturbances is observed increased blood and plasma viscosity.


Assuntos
Hemorreologia/métodos , Degeneração Macular/sangue , Degeneração Macular/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Viscosidade Sanguínea , Colesterol/sangue , Agregação Eritrocítica , Deformação Eritrocítica , Fibrinogênio/metabolismo , Hematócrito , História do Século XVI , Humanos , Pessoa de Meia-Idade , Valores de Referência , Triglicerídeos/sangue
17.
Biomed Res Int ; 2018: 9051854, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356371

RESUMO

Head and neck squamous cell cancer (HNSCC) represents a significant burden worldwide. Chemoprevention of HNSCC is a means of cancer control with a use of drugs or natural agents in order to hinder or delay the cancer development. The purpose of this article is to review mechanism of action of different chemopreventive agents' groups and results of most important researches concerning them. The safety issues of HNSCC chemoprevention are also discussed. In case of HNSCC there is currently no agent, which would give positive result in the third phase of clinical trials. Promising results of preclinical trials are not always confirmed by further tests. Main problems are low effectiveness, high toxicity, and lack of highly specificity biomarkers for monitoring the research. New trials concerning many agents, as well as novel technologies for provision of pharmaceutical forms of them, including drug nanocarriers, are currently underway, which gives hope for finding the perfect chemopreventive agent formula.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/prevenção & controle , Portadores de Fármacos/uso terapêutico , Neoplasias de Cabeça e Pescoço/prevenção & controle , Nanopartículas/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/epidemiologia , Portadores de Fármacos/efeitos adversos , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Nanopartículas/efeitos adversos
18.
Klin Oczna ; 109(7-9): 349-52, 2007.
Artigo em Polonês | MEDLINE | ID: mdl-18260296

RESUMO

Glaucoma is a kind of optic neuropathy where selective retinal ganglion cell loss is the major hallmark. Frequently glaucoma is associated with elevated intraocular pressure, but this condition is neither necessary nor sufficient for onset and progression of the disease. The exact mechanism of ganglion cell death in glaucoma and fully effective treatment of glaucomatous neuropathy still remain unknown. This article is a review of the recent researches relevant to IOP independent risk factors, mechanisms of RGC death and modern potential therapeutic strategies in glaucoma. Part one includes review of blood flow changes, neurotrophic factors deprivation and apoptotic dysregulation findings in glaucoma.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Glaucoma/complicações , Doenças do Nervo Óptico/etiologia , Células Ganglionares da Retina/patologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/uso terapêutico , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Doenças do Nervo Óptico/tratamento farmacológico
19.
Klin Oczna ; 109(7-9): 353-5, 2007.
Artigo em Polonês | MEDLINE | ID: mdl-18260297

RESUMO

Glaucoma is a kind of optic neuropathy where selective retinal ganglion cell loss is the major hallmark. Frequently glaucoma is associated with elevated intraocular pressure, but this condition is neither necessary nor sufficient for onset and progression of the disease. The exact mechanism(s) of ganglion cell death in glaucoma and fully effective treatment of glaucomatous neuropathy still remain unknown. This article reviews the recent researches relevant to IOP-independent risk factors, mechanisms of RGC death and modern potential therapeutic strategies in glaucoma. Part two includes review of ionic derangements, reactive oxygen species cytotoxicity, role of nitric oxide and immunity disorder findings in glaucoma.


Assuntos
Morte Celular , Glaucoma/patologia , Pressão Intraocular , Isquemia/metabolismo , Disco Óptico/metabolismo , Disco Óptico/patologia , Doenças do Nervo Óptico/patologia , Células Ganglionares da Retina/metabolismo , Animais , Glaucoma/complicações , Glaucoma/metabolismo , Humanos , Fármacos Neuroprotetores/metabolismo , Óxido Nítrico/metabolismo , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Retina/metabolismo , Células Ganglionares da Retina/citologia
20.
Klin Oczna ; 109(7-9): 280-2, 2007.
Artigo em Polonês | MEDLINE | ID: mdl-18260279

RESUMO

PURPOSE: To evaluate long term results of phacoemulsification with PC IOL and capsular tension ring (CTR) implantation in lens subluxation. MATERIAL AND METHODS: The study comprised of 134 patients--146 eyes with subluxated lens. In all cases phacoemulsification with PC IOL and CTR implantation was performed. RESULTS: No intaroperative complications has occured. Postoperative complications included: inflammation in the anterior chamber in 3 eyes (2.1%), retinal detachment in 2 eyes (1.4%). In all cases there was no PC IOL decentration. CONCLUSIONS: (1) CTR facilitates phacoemulsification with PC IOL implantation in lens subluxation. (2) Phacoemulsification of subluxated lens with PC IOL and CTR implantation seems to be safe and effective procedure.


Assuntos
Implante de Lente Intraocular , Subluxação do Cristalino/cirurgia , Cristalino/cirurgia , Facoemulsificação/métodos , Próteses e Implantes , Idoso , Feminino , Seguimentos , Humanos , Pressão Intraocular , Cristalino/lesões , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Implantação de Prótese , Resultado do Tratamento , Acuidade Visual
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