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Corneal activated keratocytes (CAKs) -representing the injured phenotype of corneal stromal cells- are associated with several corneal diseases. Inflammatory cytokines are the key drivers of CAK formation subsequently leading to fibrogenesis. This study aimed to investigate the effect of adlay seed extract on the expression of genes involved in inflammation (IL-6, IL-1b, LIF) and fibrogenesis (TGF-ß) in CAK cells. CAKs (106 cells/10 cm2) were exposed to methanolic (MeOH) and residual (Res) extract of adlay seed (1 mg/ml, 24 h). The control group received the vehicle solution without extract at the same time and condition. Then, RNA extraction, cDNA synthesis, and real-time PCR were performed to quantify the relative expression of IL-6, IL-1b, LIF, and TGF-ß in the treated vs. control cells. This study showed that the MeOH extract of adlay seed could significantly downregulate the expression of IL-6 and IL-1b in the CAKs, while the Res extract led to a significant decrease in TGF-ß gene expression. We showed that CAK treatment with adlay seed extract could decrease the expression of genes related to inflammation and fibrogenesis. However, the genes to be targeted depended on the method of extraction. This proof-of-concept study could provide groundwork for the treatment of corneal stromal diseases and ocular regenerative medicine in the future.
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Doenças da Córnea , Interleucina-6 , Humanos , Interleucina-6/genética , Ceratócitos da Córnea , Inflamação , Córnea , Metanol , Extratos Vegetais/farmacologiaRESUMO
PURPOSE: The purpose of this study was to investigate the prevalence of cataracts, refractive disorders, age-related macular disease (AMD), and glaucoma, as well as their trends from 1990 to 2019 in Iran, in comparison with high-middle socio-demographic index (HMSDI) countries and the world, using the Global Burden of Disease (GBD) 2019 study. METHODS: The GBD study provided data on the prevalence of blindness and visual impairment (VI), as well as four of their causes including cataracts, refractive disorders, age-related macular disease (AMD), and glaucoma. Using Joinpoint analysis, the annual percent change (APC) was calculated to assess the trend of change in prevalence in each category of diseases from 1990 to 2019, stratified by sex and age, for Iran, HMSDI countries, and the world. RESULTS: In 2019, refractive errors and cataracts were the most common causes of blindness and VI for both genders in Iran, HMSDI countries and the world. Iran had a higher age-standardized prevalence in all four categories of ophthalmologic disorders compared to HMSDI countries and the world for both genders in 2019. Additionally, the age-specific prevalence of all four disorders in 2019 was higher in Iran compared to HMSDI countries. However, in terms of trends of prevalence from 1990 to 2019, the rate of reduction for the four ophthalmologic disorders in Iran was higher than in HMSDI and the world for both males and females. Furthermore, Iran had a greater percentage of reduction in prevalence for all age groups in all four disorders compared to HMSDI countries. CONCLUSION: The prevalence of cataracts, refractive errors, AMD, and glaucoma in Iran was higher compared to HMSDI countries in 2019 for both sexes and all age groups, but the trends of prevalence for all four disorders from 1990 to 2019 in Iran had a higher slope of reduction compared to HMSDI countries for all ages and sexes.
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Catarata , Glaucoma , Degeneração Macular , Erros de Refração , Baixa Visão , Humanos , Masculino , Feminino , Carga Global da Doença , Irã (Geográfico)/epidemiologia , Prevalência , Cegueira/epidemiologia , Cegueira/etiologia , Baixa Visão/epidemiologia , Baixa Visão/etiologia , Erros de Refração/complicações , Erros de Refração/epidemiologia , Glaucoma/complicações , Glaucoma/epidemiologia , Catarata/complicações , Catarata/epidemiologia , Degeneração Macular/complicaçõesRESUMO
BACKGROUND: Scorpion envenomation, a prevalent medical emergency in rural areas, demands immediate attention due to its potential severity. While ocular manifestations are uncommon, they can lead to significant complications such as corneal ulceration. We present a unique case of corneal ulceration subsequent to a yellow scorpion (Hemiscorpius lepturus) sting near the eye, a scenario not previously documented. CASE PRESENTATION: A 34-year-old male sought medical care following a scorpion sting despite prior anti-venom treatment. Clinical examination revealed pronounced ocular inflammation, corneal stromal melting, and anterior chamber inflammation, with microbiological confirmation of Pseudomonas spp infection. Treatment comprised fortified ceftazidime and vancomycin eye drops, alongside topical corticosteroids, leading to visual and corneal healing. CONCLUSION: This case highlights the urgency of addressing scorpion envenomation and its potential for severe ocular complications, including corneal ulceration. Prompt diagnosis and targeted therapy with antibiotics and corticosteroids are crucial for favorable outcomes. A comprehensive understanding and timely intervention in scorpion sting-induced ocular manifestations are essential for optimal patient management and outcomes in such cases.
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Background: The use of honey as an eye treatment encounters challenges due to its high osmolarity, low pH, and difficulties in sterilization. This study addresses these issues by employing a low concentration of honey, focusing on both in-vitro experiments and clinical trials for treating dry eye disease in corneal cells. Methods: In the in-vitro experiment, we investigated the impact of a 1% honey-supplemented medium (HSM) on limbal stem cells (LSCs) and keratocytes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and real-time polymerase chain reaction (PCR) for BCL-2, BAX, and IL-1ß gene expression. Simultaneously, in the clinical trial, 80 participants were divided into two groups, receiving either a 1% w/v honey ophthalmic formulation or a placebo for 3 months. Study outcomes included subjective improvement in dry eye symptoms, tear break-up time (TBUT), and Schirmer's test results. Results: MTT results indicated that 1% HSM did not compromise the survival of corneal cells and significantly reduced the expression of the IL-1ß gene. Additionally, participants in the honey group demonstrated a higher rate of improvement in dry eye symptoms and a significant enhancement in TBUT values at the three-month follow-up. However, there was no significant difference between the study groups in terms of Schirmer's test values. No adverse events were observed or reported. Conclusion: In conclusion, 1% honey exhibits anti-inflammatory and anti-infective properties, proving effective in ameliorating dry eye symptoms and enhancing tear film stability in patients with dry eye disease.Clinical Trial Registration: https://irct.behdasht.gov.ir/trial/63800.
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Dry eye disease (DED) is one of the most prevalent eye diseases. This study aimed to evaluate the efficacy and safety of Latilactobacillus sakei (L. sakei) either as an ophthalmic bacterial lysate (drops, no live organism) or as an oral probiotic (capsules) on immunological and clinical outcomes of patients with DED. This study was a randomized, placebo-controlled, triple-masking clinical trial with four parallel arms. Patients were randomly assigned in a 2x2 factorial design combining active vs placebo capsules and active vs placebo eye drops in a 1:1x1:1 ratio. The ophthalmic drops are approved for use in the European Union as a medical device (CE registration code 0425-MED-004235). A total of 40 patients were evaluated. DED signs and symptoms decreased significantly by using active drops compared to placebo, as measured by the Ocular Surface Disease Index (OSDI), Tear Break-up Time (TBUT), and Schirmer I tests (all p<0.0001). Conversely, neither active capsules nor their interaction effect with active drops achieved significance vs placebo. There was also a significant decrease in the tear levels of IL-6 (p=0.0007), TNFα (p<0.0001), and IFNγ (p<0.0001) in patients receiving active drops. Intake of both active products (drops and capsules) was well tolerated. Postbiotic ophthalmic formulation containing L. sakei lysate significantly improved the signs and symptoms of DED and suppressed ocular surface inflammatory response. Conversely, oral intake of L.sakei as a probiotic capsule had no effect in these patients (ClinicalTrials.gov: NCT04938908).
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PURPOSE: Adenoviral-mediated keratoconjunctivitis is among the emergency diseases of ophthalmology with long-term sequels. The role of adenovirus infection, ocular-related genotypes, and association with ocular symptoms need to be investigated for epidemiological as well as clinical purposes. METHODS: The affected patients from two close keratoconjunctivitis epidemics were included in the study. The swab samples were taken from patients; the total DNA was extracted and then used as a template for in-house Real-time PCR. Besides, partial Hexon genes of 11 adenovirus positive samples were amplified and submitted to sanger sequencing. Moreover, they were finally evaluated by phylogenetic analysis. RESULTS: Of 153 patients, 92 (60.1%) were males and 47 cases (30.7%) had a history of eye infection in the family or colleagues. Real-time PCR tests of 126 samples (82.4%) were positive for adenovirus, and all eleven cases that underwent sequencing analysis were determined to be group 8 (HAdV-D8). Adenovirus infection has a significant relationship with infection among family or colleagues (p = 0.048), membrane formation (p = 0.047), conjunctival bleeding (p = 0.046), tearing, and pain(p < 0.05). CONCLUSIONS: The results indicated that Adenovirus is the major cause of keratoconjunctivitis, and HAdV-D8 was the most common genotype in the area. There were some clinical manifestations associated with Adenovirus infection of the conjunctiva.
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Infecções por Adenoviridae , Ceratoconjuntivite , Masculino , Humanos , Feminino , Epidemiologia Molecular , Irã (Geográfico) , Genótipo , FilogeniaRESUMO
Extracellular vesicles include exosomes, microvesicles, and apoptotic bodies. Their cargos contain a diverse variety of lipids, proteins, and nucleic acids that are involved in both normal physiology and pathology of the ocular system. Thus, studying extracellular vesicles may lead to a more comprehensive understanding of the pathogenesis, diagnosis, and even potential treatments for various diseases. The roles of extracellular vesicles in inflammatory eye disorders have been widely investigated in recent years. The term "inflammatory eye diseases" refers to a variety of eye conditions such as inflammation-related diseases, degenerative conditions with remarkable inflammatory components, neuropathy, and tumors. This study presents an overview of extracellular vesicles' and exosomes' pathogenic, diagnostic, and therapeutic values in inflammatory eye diseases, as well as existing and potential challenges.
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Micropartículas Derivadas de Células , Exossomos , Vesículas Extracelulares , Oftalmopatias , Humanos , Vesículas Extracelulares/metabolismo , Exossomos/metabolismo , Micropartículas Derivadas de Células/metabolismo , Comunicação Celular/fisiologia , Oftalmopatias/diagnóstico , Oftalmopatias/terapia , Oftalmopatias/metabolismoRESUMO
Human tears can be used as a noninvasive source of genetic materials and biomarkers in the prognosis and diagnosis of ocular and non-ocular diseases. The present protocol is a novel direct RNA extraction method from tears. This study aims to provide a suitable method for direct extraction of RNA from tears with high quality and quantity. In this study, we develop a TRIzol base protocol for direct RNA extraction from human tears. quality and quantity of extracted RNA measured by calculation of 260/280 UV absorption ratio using Nanodrop and real-time PCR. RNA was extracted with this modified method and a purified (260/280 UV absorption ratio between 1.8 to 2 and a high yield of total RNA, on average 95 µg, from tears was extracted. In conclusion, we developed an easy and suitable method for direct extraction of total RNA from tears with high quality and quantity.
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The incidence of fungal keratitis has increased in recent years. Since accurate and rapid diagnosis is important for the proper management of this infection, we evaluated the use of nested PCR to detect Aspergillus-specific DNA in corneal scrapings for the diagnosis of Aspergillus keratitis. From April 2005 to September 2008, patients with eye findings suspicious for fungal keratitis were enrolled for corneal sampling. After ocular examination, we carried out laboratory testing including direct microscopy and culture examination of corneal scrapings, nested PCR and histopathological examination of the corneal tissues obtained at surgery. Of the 57 infected eyes suspicious for fungal keratitis, 32 (56.14%) were reported as Aspergillus keratitis by PCR assay, from which 12 (37.5%) were positive in culture and direct smear for Aspergillus keratitis, and 20 (62.5%) had clinical signs of fungal keratitis (probable). All PCR-positive cases were judged to have fungal infections, based on their responses to the antifungal treatment. The use of molecular methods in high-risk patients can be helpful in diagnosis of fungal infections and can have important public health implications for both the treatment and prevention of suppurative corneal ulcerations. The significance of this study lies in the analysis of the proven cases in terms of both laboratory findings and responses to the treatment.
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Aspergillus/genética , Córnea/microbiologia , DNA Fúngico/análise , Infecções Oculares Fúngicas/diagnóstico , Ceratite/diagnóstico , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspergillus/isolamento & purificação , Criança , Córnea/patologia , Diagnóstico Diferencial , Infecções Oculares Fúngicas/metabolismo , Infecções Oculares Fúngicas/microbiologia , Feminino , Seguimentos , Humanos , Ceratite/metabolismo , Ceratite/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: The aim of this study was to evaluate the efficacy of honey-based ophthalmic drop in patients with foreign body induced corneal ulcer. BACKGROUND: Honey is traditionally used for skin, mucosal and corneal ulcers. Its use is well studied in human skin and mucosal ulcers and animal model of corneal ulcer with promising effects. METHODS: In this randomized clinical trial, 50 patients with foreign body induced corneal ulcer were allocated to receive 70% sterile honey-based ophthalmic formulation or 0.3% ophthalmic ciprofloxacin, as the standard treatment every 6 hours. All the patients were examined for the size of corneal epithelial defect, corneal infiltration and depth and followed on a daily basis until complete healing. Duration for complete healing was considered as the outcome measure. Smear, culture, antibiogram and minimum inhibition concentration (MIC) tests were performed for honey and ciprofloxacin in all patients. RESULTS: The average durations of complete healing of corneal epithelial defect in the honey and ciprofloxacin groups were 3.88 ± 3.44 vs. 6.32 ± 3.69days, respectively (p=0.020). No significant difference was observed between two groups regarding an average duration of healing of corneal infiltration (8.12 ±1.94 days vs. 8.64±2.15 days, p=0.375). MIC of honey for pseudomonas aeruginosa was 60%w/w, for E.Coli 40% w/w, and for staphylococcus aureus 30% w/w. CONCLUSION: Honey based ophthalmic drop can acceleratethe corneal epithelial defect healing in patients with foreign body induced corneal ulcer, compared to ophthalmic ciprofloxacin as a standard treatment. The study was registered in Iranian registry of clinical trial center (IRCT) with registration number IRCT2015020120892N1.
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Apiterapia/métodos , Úlcera da Córnea/tratamento farmacológico , Corpos Estranhos no Olho/complicações , Mel , Cicatrização/efeitos dos fármacos , Adulto , Ciprofloxacina/administração & dosagem , Úlcera da Córnea/etiologia , Corpos Estranhos no Olho/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVE: This study seeks to evaluate the efficacy and practicality of the molecular method, compared to the standard microbiological techniques for diagnosing fungal keratitis (FK). METHODS: Patients with eye findings suspected of FK were enrolled for cornea sampling. Scrapings from the affected areas of the infected corneas were obtained and were divided into two parts: one for smears and cultures, and the other for nested PCR analysis. RESULTS: Of the 38 eyes, 28 were judged to have fungal infections based on clinical and positive findings in the culture, smear and responses to antifungal treatment. Potassium hydroxide, Gram staining, culture and nested PCR results (either positive or negative) matched in 76.3, 42.1, 68.4 and 81.6%, respectively. CONCLUSION: PCR is a sensitive method but due to the lack of sophisticated facilities in routine laboratory procedures, it can serve only complementarily and cannot replace conventional methods.
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Técnicas Bacteriológicas , Úlcera da Córnea/diagnóstico , Infecções Oculares Fúngicas/diagnóstico , Fungos/citologia , Fungos/genética , Violeta Genciana , Fenazinas , Reação em Cadeia da Polimerase , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspergillus fumigatus/citologia , Aspergillus fumigatus/genética , Candida albicans/citologia , Candida albicans/genética , Criança , Úlcera da Córnea/microbiologia , DNA Fúngico/análise , Infecções Oculares Fúngicas/microbiologia , Feminino , Fusarium/citologia , Fusarium/genética , Humanos , Hidróxidos , Masculino , Pessoa de Meia-Idade , Compostos de Potássio , Coloração e Rotulagem , Adulto JovemRESUMO
PURPOSE: To evaluate the effectiveness of ultraviolet (UV)-A/Riboflavin corneal cross-linking (CXL) for the treatment of the refractory cases of fungal keratitis. METHODS: In this prospective interventional study, 9 patients with the diagnosis of fungal keratitis that were referred to our emergency eye center were included. These patients were resistant to conventional treatment and underwent therapeutic UV-A/Riboflavin CXL. Response to the treatment was considered as good if rapid epithelialization and rapid decrease in stromal infiltration was occurred after PACK-CXL, and poor when the emergency transplantation was necessary to eradicate the infection. RESULTS: Nine patients treated with CXL due to recalcitrant fungal keratitis. Culture of the corneal scrapings showed Aspergillus species in 4 patients, Candida albicans in 1 patient and Fusarium species in the remainder of them. CXL was performed from 1 to 20 days after the presentation of corneal ulcers (Mean: 9.12 ± 4.02; range: 5-20 days). Postoperatively, the mean time to epithelialization was 14.25 ± 2.38 days, and mean time to resolution of stromal infiltration was 22.5 ± 7.29 days, in responsive cases. Four out of 9 eyes showed good response, and five patients showed no response, and corneal transplantation was performed to eradicate the infection. There was no statistically significant difference in mean depth of infiltration and mean size of ulcer between responsive and unresponsive patients (P = 0.86 and 0.08, respectively). CONCLUSION: Although UV-A/Riboflavin CXL is not a definite treatment for all of the fungal keratitis, it seems promising in the management of some refractory cases.
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Colágeno/metabolismo , Úlcera da Córnea/tratamento farmacológico , Reagentes de Ligações Cruzadas , Infecções Oculares Fúngicas/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Adulto , Idoso , Substância Própria/metabolismo , Úlcera da Córnea/metabolismo , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/metabolismo , Infecções Oculares Fúngicas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/métodos , Estudos Prospectivos , Microscopia com Lâmpada de Fenda , Raios UltravioletaRESUMO
Introduction: This study was conducted to compare the effect of nanofibrous polycaprolactone (PCL) and PCL/gelatin (PCL/Gel) on limbal epithelial stem cell (LESC) and its efficiency for transplantation in animal model. Methods: PCL and PCL/Gel with a mass ratio of 70:30 and 50:50 was fabricated by electrospinning method. Human LESCs were cultured on PCL and PCL/Gel scaffolds and the effect of each scaffold on LESC proliferation, attachment and corneal epithelial regeneration in an animal model was evaluated, considering ease of use of scaffold and final transparency of the cornea. Results: Our data showed that PCL was more suitable than PCL/Gel for LESCs adherence, induction of epithelial morphology and proliferation. Histopathologic analysis of corneal sections from transplanted animals showed that epithelium was regenerated almost similar in PCL and PCL/Gel groups; however, vascularization and inflammation were significantly lower in the group receiving PCL. Conclusion: The represented data indicated the priority of PCL to PCL/Gel for the LESC attachment, proliferation and final outcome in an animal model of alkaline injury. This finding might be promising for cell therapy of corneal diseases.
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BACKGROUND: Dry eye disease is a disorder of the tear film. In this study, the effect of Viola odorata L. oily extract was examined for the treatment of patients suffering from dry eye disease. METHODS: A randomised, double-blind, placebo-controlled study was designed. During the trial, Schirmer's test, tear breakup time, Oxford staining and the Ocular Surface Disease Index were assessed. Overall, 105 patients with dry eye symptoms between the ages of 18 and 60 years were allocated to the violet-almond oil, almond oil and placebo (1% w/v hydroxypropyl methylcellulose solution) groups. The treatment and placebo were administered intranasally, two drops three times a day for one month. The patients were followed up for four weeks. A total of 91 patients (32, 29 and 30 in the violet-almond oil, almond oil and placebo groups, respectively) completed the study. RESULTS: At baseline, there was no difference between the three groups in terms of demographic data and the measurement parameters. After the intervention, the results revealed that the Schirmer's score without local anaesthesia and the tear breakup time results significantly improved in the violet-almond oil group. One-way ANOVA indicated a significant improvement in the Schirmer's score, tear breakup time and Ocular Surface Disease Index of the treatment group, as compared with the other groups (p < 0.05). However, the obtained results did not present any significant mean difference between and within the groups of the Oxford staining grade (p > 0.05). CONCLUSIONS: This trial showed that the intranasally administered V. odorata L. oily extract enhances tear production and improves tear film stability.
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Síndromes do Olho Seco/tratamento farmacológico , Óleos de Plantas/administração & dosagem , Lágrimas , Viola/química , Administração Intranasal , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Pterygium is one of the most common eye conditions without any clear etiology. Some studies have suggested an association between sun exposure and pterygium, but others have proposed the role of genetic variations in its pathogenesis. To date, no study has investigated the association of inflammatory transcription factor, NFκB genes with pterygium in the Middle East. We examined the changes in expression of 3 inflammatory related NFκB1, NFκB2, and RELA genes in patients with pterygium. Thirty patients with pterygium and 30 age and sex-matched controls were enrolled in this case-control study. None of the participants showed any clinical signs of inflammation in their conjunctiva. Demographic information was obtained and the expression levels of three genes including NFκB1, NFκB2, and RELA were measured in their conjunctiva by real-time RT-PCR using gene-specific primers. Mean expression level of NFκB1, NFκB2 and RELA genes in patients were 2.4±0.3, 1.9± 0.5, and 1.8±0.4 times higher than normal subjects, respectively. Higher levels of gene expression were observed in individuals with more outdoor activity and sun exposure. Moreover, a significant correlation was observed between the expression levels of NFκB2 and RELA genes, suggesting a possible NFκB2- RELA heterodimer formation in patients with pterygium. This study has indicated a significant association between expressions of inflammatory-related NFκB1, NFκB2 and RELA genes, and pterygium. Further studies to verify the role of inflammation in the pathogenesis of pterygium, may provide new targets for managing pterygia.
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The factors triggering corneal neovascularization involve various growth factors. The data supporting a causal role for vascular endothelial growth factor (VEGF) in corneal neovascularization are extensive. One possible strategy for treating corneal neovascularization is to inhibit VEGF activity by competitively binding VEGF with a specific neutralizing anti-VEGF antibody. The vireo-retinal service in the recent years enjoyed a high level of success in managing choroidal neovascularization using anti-VEGF strategies. Efficacy and tolerability have been demonstrated for drugs targeting VEGF. We herein hypothesize that topical application of new anti-VEGF agents such as pegaptanib, ranibizumab and bevacizumab are potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations are needed to place these medical treatments alongside corneal neovascularization therapeutics.
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Inibidores da Angiogênese/farmacologia , Córnea/irrigação sanguínea , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/patologia , Vasos Retinianos/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Ligação Competitiva , Humanos , Inflamação , Modelos Biológicos , Modelos Cardiovasculares , Modelos TeóricosRESUMO
In the last two decades of angiogenesis research, a variety of angiogenic regulators have been identified. The discovery of several antiangiogenic factors has led to the development of novel ophthalmic therapies. Pterygia are characterized by the encroachment of a fleshy fibrovascular tissue from the bulbar conjunctiva onto the cornea. The pathogenesis of pterygia is presently uncertain and its treatment is quiet controversial. It has also been postulated that the development of pterygia depends on a changed angiogenic stimulator-to-inhibitor ratio. On of the most important known mediators of angiogenesis in pterygia is vascular endothelial growth factor (VEGF). In this article, we briefly review the evidences supporting involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of pterygia and then based on these evidences, we hypothesize that local application of bevacizumab, a monoclonal antibody against VEGF, may inhibit neovascularization and thus, may stop the progression or prevent the recurrence of pterygia.
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Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Pterígio/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Bevacizumab , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Pterígio/fisiopatologiaRESUMO
PURPOSE: To investigate mutations of visual system homeobox 1 (VSX1) and superoxide dismutase 1 (SOD1) in 20 patients with keratoconus in the south of Iran. METHODS: Twenty patients with keratoconus who had a positive familial history were enrolled in this study and gave informed consent for DNA analysis. Genomic DNA was extracted from peripheral blood lymphocytes. Polymerase chain reaction (PCR) was carried out to amplify exon 2 of SOD1 and its exon-intron boundary for the detection of a seven-base deletion in intron 2 of SOD1, and also all five exons of VSX1 and their exon-intron boundaries. Amplified samples were then subjected to direct DNA sequencing. RESULTS: Sequencing data were compared against reference sequences using NCBI basic local alignment search tool (BLAST), which revealed that our patients had no mutations in SOD1 and VSX1. Two single-nucleotide polymorphisms (SNPs), namely in VSX1(rs58752432 and rs59089167) were found in six patients. CONCLUSION: Mutations in VSX1 and SOD1 genes associated with keratoconus were not identified in our patients. Therefore, it will be necessary to investigate other chromosomal loci for potential causal mutations of keratoconus using next generation sequencing (NGS) methods in our population.
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INTRODUCTION: With an incidence rate of 9%, dry eye is a common problem of the ocular surface, especially in patients more than 40-year-old. Green tea extract has anti-oxidative, anti-bacterial, anti-androgen, and immunomodulatory properties. AIM: To evaluate the efficacy of green tea extract for treatment of patients with dry eye and Meibomian Gland Dysfunction (MGD). MATERIALS AND METHODS: In a double-blind randomized controlled clinical trial, 60 patients were selected within the age range of 30 to 70 years, and divided into two groups by blocked randomization method. Standard treatment included artificial tear eye drops, three times a day for a month for all patients. Topical green tea extract was prescribed three times a day for one month in one of the groups. All patients were evaluated at the beginning and end of the study for clinical symptoms based on the Ocular Surface Disease Index (OSDI) score, Schirmer's test, Tear Breakup Time (TBUT), corneal and conjunctival staining and meibum score. RESULTS: The mean age of participants in the green tea and control group was 61 and 64 years respectively. In the green tea group, the mean score of clinical symptoms was 9±0.86 that improved to 4.86±0.55 after one month (p=0.002). Scores suggesting improvement of TBUTs and the health of meibomian glands were significantly higher in the green tea group (p=0.002). Furthermore, no side effects of the treatment were observed. CONCLUSION: Green tea extract is an effective, safe, and well-tolerated topical treatment for mild and moderate evaporative dry eyes and MGD.
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Purpose: To test candidate genes TSC1 and TSC2 in a family affected by tuberous sclerosis complex (TSC) where proband was also diagnosed with bilateral keratoconus (KC) and to test the hypothesis that defects in the same gene may lead to a nonsyndromic KC. Methods: Next-generation sequencing of TSC1 and TSC2 genes was performed in a proband affected by TSC and KC. Identified mutation was confirmed by Sanger DNA sequencing. Whole exome sequencing (WES) was performed in patients with nonsyndromic KC. Sanger DNA sequencing was used to confirm WES results and to screen additional patients. RT-PCR was used to investigate TSC1 expression in seven normal human corneas and eight corneas from patients with KC. Various in silico tools were employed to model functional consequences of identified mutations. Results: A heterozygous nonsense TSC1 mutation g.132902703C>T (c.2293C>T, p.Gln765Ter) was identified in a patient with TSC and KC. Two heterozygous missense TSC1 variants g.132896322A>T (c.3408A>T, p.Asp1136Glu) and g.132896452G>A (c.3278G>A, p.Arg1093Gln) were identified in three patients with nonsyndromic KC. Two mutations were not present in The Genome Aggregation (GnomAD), The Exome Aggregation (ExAC), and 1000 Genomes (1000G) databases, while the third one was present in GnomAD and 1000G with minor allele frequencies (MAF) of 0.00001 and 0.0002, respectively. We found TSC1 expressed in normal corneas and KC corneas, albeit with various levels. Conclusions: Here for the first time we found TSC1 gene to be involved in bilateral KC and TSC as well as with nonsyndromic KC, supporting the hypothesis that diverse germline mutations of the same gene can cause genetic disorders with overlapping clinical features.