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1.
J Ophthalmol ; 2024: 6653621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827421

RESUMO

Purpose: Our study aimed to evaluate the indications and outcomes of intraocular lens (IOL) explantation surgeries in a tertiary eyecare center in Hungary. Materials and Methods: This retrospective study included all IOL explantation surgeries performed between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University, Budapest, Hungary. There were no exclusion criteria for this study. For each patient, the demographics, clinical history, preoperative status, indications for IOL explantation, and operative and postoperative details were reviewed. Primary outcomes included explantation indications and the type of secondary implanted IOL. Results: A total of 161 eyes from 153 patients were included (96 males; 62.7%); age at the time of the IOL explantation was 65.0 ± 17.4 years. The mean time between primary cataract surgery and IOL explantation was 8.5 ± 7.7 years. In total, 139 (86.3%) PCIOLs and 22 (13.7%) ACIOLs were explanted. The main indications for IOL explantation were dislocation (n = 133; 95.7%) and refractive cause (n = 2; 1.4%) in the PCIOL group. Among ACIOL explantations, the main reasons were pseudophakic bullous keratopathy (n = 14; 63.6%), dislocation (n = 4; 18.2%), and refractive cause (n = 2; 9.1%). In the PCIOL group, 115 (82.7%) primary IOLs were implanted in the capsular bag, 16 (11.5%) were sulcus fixated, and 8 (5.8%) were scleral fixated. The most frequent ocular comorbidities were previous vitrectomy (n = 50, 31.1%), previous ocular trauma (n = 45, 28.0%), glaucoma (n = 16, 9.9%), pseudoexfoliation syndrome (n = 15, 9.3%), and high axial myopia (n = 14, 8.7%). The most commonly used secondary IOL implant was the prepupillary iris-claw IOL (n = 115, 73.7%), followed by the retropupillary iris-claw IOL (n = 32, 20.5%). Uncorrected visual acuity (UCVA) was significantly better following IOL exchange in the entire sample (1.57 ± 0.61 (range: 2.40-0.05) vs. 0.77 ± 0.56 (range: 2.40-0.00); p < 0.001). Best-corrected visual acuity (BCVA) was maintained or improved in 80.7% of cases after IOL explantation. Conclusions: The most common indication for IOL explantation at a tertiary eyecare center in Hungary is IOL dislocation, followed by pseudophakic bullous keratopathy. Prepupillary and retropupillary iris-claw IOL are the most frequently used secondary implants and their use resulted in a significant UCVA improvement following IOL exchange.

2.
Ophthalmol Ther ; 13(5): 1343-1356, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38507192

RESUMO

INTRODUCTION: This study analysed the causative factors and clinical characteristics of acute and chronic ocular sequelae of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) treated at a large third-referral centre in a developed country (Hungary) over a 15-year period. METHODS: This was a retrospective review of patients with acute and/or chronic SJS/TEN who were managed between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University in Budapest, Hungary. For each subject, clinical data, including patient demographics, clinical history, causative agents of SJS/TEN, and conservative and surgical treatment details, were reviewed. RESULTS: Ninety-six eyes of 48 patients were included (28 female; 58.3%); the age at disease onset was 32.1 ± 22.4 years. The most common causative factors were medicines (n = 36; 75.0%). Among these drugs, 29.2% were nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 14), 20.8% were antibiotics (n = 10) and 14.6% were antiepileptic drugs (n = 7). In patients with chronic SJS/TEN, the most commonly found ocular sequelae were conjunctival hyperaemia in 45 (56.3%) eyes, symblepharon in 38 (47.5%) eyes, trichiasis/distichiasis in 37 (46.3%) eyes, corneal neovascularization in 31 (38.8%) eyes and corneal scarring in 29 (36.3%) eyes. In patients with chronic SJS/TEN, the most frequently used topical conservative treatment included antibiotics in 53 (66.3%) eyes, preservative-free artificial tears in 50 (62.5%) eyes and topical corticosteroids in 42 (52.5%) eyes of 40 patients. The most frequently performed ocular surgeries for managing chronic ocular sequelae in patients with SJS/TEN were epilation for trichiasis (n = 27; 33.8%), cataract surgery (n = 14; 17.5%), entropion surgery (n = 12; 15.0%), penetrating keratoplasty (PK) (n = 11; 13.8%) and amniotic membrane transplantation (n = 4; 5.0%). CONCLUSION: Our results suggest that NSAIDs, antibiotics and antiepileptic drugs are the most common causative factors for SJS/TEN in Hungary. Like in other countries, in Hungary, the ocular management of patients with acute and chronic SJS/TEN is heterogeneous, and most cases do not follow modern therapeutic guidelines.

3.
Ophthalmol Ther ; 12(4): 1795-1811, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37140876

RESUMO

The aim of our review article was to summarize the current literature on Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN). SJS/TEN is a serious, rare multi-system, immune-mediated, mucocutaneous disease with a significant mortality rate that can lead to severe ocular surface sequelae and even to bilateral blindness. Restoration of the ocular surface in acute and chronic SJS/TEN is challenging. There are only limited local or systemic treatment options for SJS/TEN. Early diagnosis, timely amniotic membrane transplantation and aggressive topical management in acute SJS/TEN are necessary to prevent long-term, chronic ocular complications. Although the primary aim of acute care is to save the life of the patient, ophthalmologists should regularly examine patients already in the acute phase, which should also be followed by systematic ophthalmic examination in the chronic phase. Herein, we summarize actual knowledge on the epidemiology, aetiology, pathology, clinical appearance and treatment of SJS/TEN.

4.
Sensors (Basel) ; 13(3): 3753-64, 2013 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-23507821

RESUMO

PURPOSE: The purpose of the study was to implement a new eye tracking mask which could be used to guide the laser beam in automated non-mechanical excimer laser assisted penetrating keratoplasty. MATERIALS AND METHODS: A new trephination mask design with an elevated surface geometry has been proposed with a step formation between conical and flat interfaces. Two recipient masks of 7.5/8.0 mm have been manufactured and tested. The masks have outer diameter of 12.5 mm, step formation at 10.5 mm, and slope of conical surfaces 15°. Its functionality has been tested in different lateral positions and tilts on a planar surface, and pig eye experiments. After successful validation on porcine eyes, new masks have been produced and tested on two patients. RESULTS: The build-in eye tracking software of the MEL 70 was always able to capture the masks. It has been shown that the unwanted pigmentation/pattern induced by the laser pulses on the mask surface does not influence the eye-tracking efficiency. The masks could be tracked within the 18 × 14 mm lateral displacement and up to 12° tilt. Two patient cases are demonstrated. No complications were observed during the surgery, although it needs some attention for aligning the mask horizontally before trephination. Stability of eye tracking masks is emphasized by inducing on purpose movements of the patient head. CONCLUSION: Eye-tracking-guided penetrating keratoplasty was successfully applied in clinical practice, which enables robust tracking criteria within an extended range. It facilitates the automated trephination procedure of excimer laser-assisted penetrating keratoplasty.


Assuntos
Córnea/cirurgia , Ceratoplastia Penetrante/instrumentação , Lasers de Excimer , Máscaras , Animais , Humanos , Ceratoplastia Penetrante/métodos , Complicações Pós-Operatórias/cirurgia , Suínos
5.
Cornea ; 32(2): 111-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22580432

RESUMO

PURPOSE: To present light and electron microscopic as well as immunohistochemical findings after corneal cross-linking (CXL). METHODS: Six keratoconus corneas after CXL, 12 keratoconus corneas without CXL, and 7 normal corneas were examined by light microscopy, indirect immunohistochemistry using antibodies against proapoptotic BAX, antiapoptotic survivin, and BCL-2, and anti-smooth muscle actin and, in part, by transmission electron microscopy. Direct immunofluorescence with 4'6-diamidino-2-phenylindole was performed to analyze keratocytes/area in the anterior, middle, posterior, peripheral, and central corneal stroma. RESULTS: The period between CXL and keratoplasty ranged from 5 to 30 months. All keratoconus corneas showed the typical histological changes. Increased proapoptotic BAX expression and/or antiapoptotic survivin expression were noticed in keratocytes and endothelium in 2 keratoconus specimens after CXL. Smooth muscle actin was only observed in subepithelial scar tissue of 2 keratoconus corneas without CXL. Keratoconus corneas after CXL revealed a significant reduction in keratocyte counts in the entire cornea (P = 0.003) compared with keratoconus corneas without CXL and normal corneas. This difference was because of a loss of keratocytes in the anterior (P = 0.014) and middle (P = 0.024) corneal stroma. Keratocytes in CXL corneas were reduced in the center (P = 0.028) and the periphery (P = 0.047). CONCLUSIONS: CXL in human keratoconus can cause considerable morphologic corneal changes up to 30 months postoperatively. Especially noteworthy is a long-lasting, maybe permanent, keratocyte loss in the anterior and middle corneal stroma involving the central and peripheral cornea. As long-term corneal damage after CXL is of genuine concern, particular care should be taken to perform this procedure only in accordance with investigational protocols.


Assuntos
Biomarcadores/metabolismo , Colágeno/metabolismo , Substância Própria/metabolismo , Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/metabolismo , Ceratocone/patologia , Actinas/metabolismo , Adolescente , Adulto , Ceratócitos da Córnea/metabolismo , Ceratócitos da Córnea/ultraestrutura , Feminino , Técnica Direta de Fluorescência para Anticorpo , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Ceratocone/terapia , Ceratoplastia Penetrante , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Riboflavina/uso terapêutico , Survivina , Raios Ultravioleta , Adulto Jovem , Proteína bcl-X/metabolismo
6.
Graefes Arch Clin Exp Ophthalmol ; 251(3): 797-802, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22850977

RESUMO

BACKGROUND: To evaluate the trends in indications for penetrating keratoplasty (PKP) in Homburg/Saar between 2001 and 2010. METHODS: Retrospective review of 1,200 corneal buttons which underwent PKP that were performed between 2001 and 2010 at the Department of Ophthalmology of Saarland University Hospital, Germany. Indications were classified into eight different groups following histological analysis: keratoconus, Fuchs' dystrophy, bullous keratopathy, corneal scars, keratitis, regraft, corneal dystrophy other than Fuchs' dystrophy, and other diagnoses. Two different time periods (between 2001-2005 and between 2006-2010) were analyzed. RESULTS: Keratoconus (25.5 %) was the most common indication for PKP in our study, followed by Fuchs' dystrophy (21.2 %), bullous keratopathy (14.6 %), corneal scars (14.4 %), keratitis (13.0 %), regraft (7.0 %), non-Fuchs' dystrophies (2.1 %), and other diagnoses (2.3 %). Comparing the two different time periods, a trend of significantly increasing frequency of keratoconus and Fuchs' dystrophy, and a decreasing frequency of corneal scars, were found as indications for PKP in our study. CONCLUSIONS: Keratoconus was the leading indication for PKP in our series, and had a significantly increasing trend from 2001-2005 to 2006-2010. The percentage of patients with Fuchs' dystrophy increased, and became the second most common indication for PKP, while the number of PKPs for corneal scars decreased during the last 5 years in our institution.


Assuntos
Doenças da Córnea/epidemiologia , Doenças da Córnea/patologia , Ceratoplastia Penetrante/tendências , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Doenças da Córnea/cirurgia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Adulto Jovem
8.
J Cataract Refract Surg ; 35(4): 778-81, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19304105

RESUMO

We report the case of a 68-year-old man who developed bilateral Descemet membrane detachment (DMD) 4 weeks after successful cataract surgery and discuss the possible role of an underlying predisposition to DMD. Surgical intervention with gas injection in the anterior chamber resulted in excellent visual acuity restoration in the patient. To our knowledge, this is the first report of spontaneous bilateral DMD in the late postoperative period after cataract extraction.


Assuntos
Edema da Córnea/etiologia , Lâmina Limitante Posterior/patologia , Facoemulsificação , Complicações Pós-Operatórias , Idoso , Câmara Anterior/efeitos dos fármacos , Edema da Córnea/terapia , Topografia da Córnea , Humanos , Implante de Lente Intraocular , Masculino , Ruptura Espontânea , Hexafluoreto de Enxofre/administração & dosagem
9.
Invest Ophthalmol Vis Sci ; 49(5): 1797-808, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18436814

RESUMO

PURPOSE: The purpose of the study was to test the hypothesis that estrogen and progesterone regulate gene expression in the meibomian gland. METHODS: Meibomian glands were obtained from young adult, ovariectomized mice that were administered 17beta-estradiol, progesterone, 17beta-estradiol plus progesterone, or vehicle for 14 days. Glands were pooled according to treatment, processed for the extraction of RNA, and analyzed for differentially expressed mRNAs by using mouse gene microarrays. Bioarray data were evaluated with sophisticated bioinformatics software and statistical programs. The expression of selected genes was confirmed with gene chips and quantitative real-time PCR techniques. RESULTS: The findings show that 17beta-estradiol, progesterone, or both hormones administered together significantly influenced the expression of numerous genes in the mouse meibomian gland. Notable were the effects of 17beta-estradiol on genes related to lipid metabolism, tyrosine kinases, immune factors, extracellular matrix components, steroidogenesis, and prolactin dynamics. Also very significant were the actions of progesterone or 17beta-estradiol plus progesterone on ribosome or localization gene ontologies, respectively. The various hormone treatments led to many analogous, opposite, or unique effects on gene expression. CONCLUSIONS: These findings support the study hypothesis that estrogen and progesterone modulate gene expression in the meibomian gland.


Assuntos
Estradiol/farmacologia , Estrogênios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glândulas Tarsais/metabolismo , Progesterona/farmacologia , Progestinas/farmacologia , Animais , Combinação de Medicamentos , Proteínas do Olho/genética , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Ovariectomia , RNA Mensageiro/metabolismo
10.
Curr Eye Res ; 32(5): 393-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17514523

RESUMO

PURPOSE: We tested our hypothesis that testosterone increases the meibomian gland gene expression of numerous enzymes in the cholesterol biosynthetic pathway. METHODS: Meibomian glands were obtained from castrated mice treated with vehicle or testosterone for 2 weeks. Tissues were processed for the analysis of selected mRNAs by real-time PCR. RESULTS: Our research demonstrates that testosterone stimulates a significant increase in the mRNA levels of mevalonate kinase, phosphomevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl pyrophosphate isomerase, geranylgeranyl pyrophosphate synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and Delta 7-sterol reductase. CONCLUSIONS: Our findings indicate that androgens may promote cholesterol biosynthesis in the meibomian gland.


Assuntos
Colesterol/biossíntese , Enzimas/genética , Enzimas/metabolismo , Glândulas Tarsais/metabolismo , RNA Mensageiro/metabolismo , Testosterona/farmacologia , Animais , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
11.
Ophthalmology ; 113(10): 1758-64, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17011956

RESUMO

PURPOSE: To compare the sensitivity, specificity, and accuracy of the RPS Adeno Detector (Rapid Pathogen Screening Inc., South Williamsport, PA) against both viral cell culture with confirmatory immunofluorescence staining (CC-IFA) and the polymerase chain reaction (PCR) for diagnosing adenoviral conjunctivitis. DESIGN: Prospective, nonrandomized, masked, multicenter clinical trial. PARTICIPANTS: One hundred eighty-six consecutive patients from 5 clinical centers seeking treatment within 1 week of developing a red eye and thought to have acute conjunctivitis. METHODS: The RPS Adeno Detector is a 10-minute in-office lateral flow immunoassay. Patients were tested with the RPS Adeno Detector, CC-IFA, and PCR to detect the presence of adenovirus. MAIN OUTCOME MEASURES: The sensitivity, specificity, and accuracy of the RPS Adeno Detector were assessed for identifying cases of adenoviral conjunctivitis. RESULTS: Compared with CC-IFA, the RPS Adeno Detector was 88% sensitive and 91% specific at detecting adenoviral conjunctivitis. Using PCR as a reference method, the sensitivity of the RPS Adeno Detector increased to 89% and the specificity increased to 94%. Compared with PCR, CC-IFA was found to be 91% as sensitive and 100% as specific. CONCLUSIONS: The RPS Adeno Detector demonstrated sufficient sensitivity and specificity to be used in the physician's office for the detection of adenoviral conjunctivitis.


Assuntos
Infecções por Adenovirus Humanos/diagnóstico , Adenovírus Humanos/isolamento & purificação , Conjuntivite Viral/diagnóstico , Técnicas Imunológicas , Reação em Cadeia da Polimerase , Doença Aguda , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/genética , Adenovírus Humanos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/análise , Criança , Pré-Escolar , Conjuntivite Viral/virologia , DNA Viral/análise , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Lágrimas/virologia , Cultura de Vírus
12.
Cornea ; 25(4): 438-42, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16670482

RESUMO

PURPOSE: Sex steroids exert a significant influence on the health and well-being of the ocular surface and adnexa. These hormones affect multiple aspects of the lacrimal and meibomian glands, conjunctiva, and cornea, and have been linked to the development of many ocular surface pathologies. We hypothesize that these hormone actions, as in other tissues, occur predominantly after the local synthesis of androgens and estrogens from adrenal precursors. To begin to test this hypothesis, we analyzed whether human ocular surface and adnexal tissues and cells contain the steroidogenic enzyme mRNAs necessary for the intracrine synthesis and metabolism of sex steroids. METHODS: Total RNA was isolated from human lacrimal and meibomian glands and immortalized corneal and conjunctival epithelial cells. Samples were reverse transcribed to cDNA and analyzed for the presence of enzyme mRNAs by real-time PCR. Positive and negative controls included human placental cDNA and the absence of template, respectively. RESULTS: Our results show that human lacrimal and meibomian glands and corneal and conjunctival epithelial cells contain the mRNAs for steroid sulfatase, 3beta-hydroxysteroid dehydrogenase (HSD)-Delta-Delta-isomerase type 1, 17beta-HSD types 1 and 3, aromatase, and glucuronosyltransferase. In contrast, only lacrimal and meibomian tissues appeared to contain detectable mRNA for sulfotransferase. CONCLUSIONS: If the corresponding mRNAs are translated, our results indicate that human ocular surface and adnexal tissues contain the enzymatic machinery necessary for the intracrine synthesis and metabolism of sex steroids.


Assuntos
Túnica Conjuntiva/enzimologia , Córnea/enzimologia , Enzimas/genética , Aparelho Lacrimal/enzimologia , Glândulas Tarsais/enzimologia , RNA Mensageiro/metabolismo , 17-Hidroxiesteroide Desidrogenases/genética , Idoso , Idoso de 80 Anos ou mais , Aromatase/genética , Feminino , Glucuronosiltransferase/genética , Hormônios Esteroides Gonadais/biossíntese , Humanos , Masculino , Complexos Multienzimáticos/genética , Progesterona Redutase/genética , Esteroide Isomerases/genética , Esteril-Sulfatase/genética
13.
Exp Eye Res ; 83(2): 291-6, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16579987

RESUMO

We hypothesize that androgens regulate lipogenesis in the meibomian gland. To test this hypothesis, we sought to determine whether androgens increase the mRNA levels of key lipogenic enzymes involved in the synthesis of cholesterol and fatty acids. In addition, we examined whether androgens stimulate the expression of genes for sterol regulatory element binding proteins (SREBP) 1 and 2, which are transcription factors that play an important role in the coordinate regulation of lipogenic enzymes. Meibomian glands were obtained from castrated mice, that were treated with vehicle or testosterone for 2 weeks. Tissues were processed for the analysis of selected mRNAs by real-time PCR. Our results show that testosterone increases the mRNA levels of critical lipogenic enzymes, including those related to ATP-citrate lyase, acetyl-CoA-synthase, acetyl-CoA-carboxylase, acetoacetyl-CoA-synthase and 3-hydroxy-3-methylglutaryl CoA synthase 1. Our findings also demonstrate that androgens upregulate the expression of genes encoding the transcription factors SREBPs 1 and 2. Our results indicate that androgens may control multiple aspects of lipogenesis in the meibomian gland.


Assuntos
Androgênios/metabolismo , Lipogênese/fisiologia , Glândulas Tarsais/metabolismo , Androgênios/farmacologia , Animais , Colesterol/biossíntese , Ácidos Graxos/biossíntese , Regulação da Expressão Gênica/genética , Masculino , Glândulas Tarsais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análise , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Testosterona/farmacologia , Regulação para Cima/genética
14.
Curr Eye Res ; 31(2): 119-28, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16500762

RESUMO

PURPOSE: Sex-related differences have been identified in the anatomy and physiology of the meibomian gland. We hypothesize that these differences are due, at least in part, to variations in gene expression. This study's objective was to determine whether sex-related differences do exist in meibomian gland gene expression. We also sought to elucidate whether such differences, if any, might be (a) analogous to those known to occur in the lacrimal gland and (b) due to the effect of sex steroids. METHODS: Meibomian glands were obtained from young adult male and female BALB/c mice (n=7 to 15 mice per sex per experiment), pooled according to sex and processed for the isolation of RNA. Samples were evaluated for differentially expressed mRNAs by using CodeLink Bioarrays and GEM 1 and 2 gene chips. Bioarray data were analyzed with GeneSifter. Net software and also compared with microarray data in GEO and GeneSifter databases. RESULTS: Our results demonstrate that sex has a significant influence on the expression of 164 genes in the mouse meibomian gland. These genes are involved in a broad spectrum of biological processes, molecular functions, and cellular components, including such activities as metabolism, catalysis, cell growth and maintenance, membrane architecture, nucleic acid binding, transcription, and signal transduction. In addition, the nature of the sex-related variations in meibomian gland gene expression is quite different from those in the lacrimal gland and appear to be mediated in part by the action of androgens, but not estrogens or progestins. CONCLUSIONS: These findings support our hypothesis that sex-related differences exist in gene expression of the meibomian gland.


Assuntos
Proteínas do Olho/genética , Regulação da Expressão Gênica/fisiologia , Glândulas Tarsais/metabolismo , RNA Mensageiro/metabolismo , Caracteres Sexuais , Animais , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos
15.
Exp Eye Res ; 82(1): 13-23, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15979613

RESUMO

Significant, sex-associated differences exist in the physiology and pathophysiology of the lacrimal gland. We hypothesize that many of these differences are due to fundamental variations in gene expression. The purpose of this study was to determine the extent to which sex-related differences in gene expression are present in the lacrimal gland. Lacrimal glands were obtained from adult male and female BALB/c mice (n=5-10mice/sex/experiment), pooled according to sex and processed for the isolation of RNA. Samples were analyzed for differentially expressed mRNAs by using Atlas Mouse cDNA Expression Arrays, cDNA amplification techniques, GEM 1 and 2 gene chips, CodeLink bioarrays and quantitative real-time PCR (qPCR) procedures. Quantitative evaluation of Atlas Array gene expression was performed with an image analysis system developed in our laboratory, whereas gene chip data were analyzed with Rosetta Resolver and GeneSifter.Net software. Statistical significance was determined by using Student's t-test. Our results with CodeLink bioarrays show that sex has a significant influence on the expression of over 490 genes in the mouse lacrimal gland. These genes are involved in a wide range of biological processes, molecular functions and cellular components, including such activities as development, growth, transcription, metabolism, signal transduction, transport, receptor activity and protein and nucleic acid binding. The expression of selected genes was confirmed by the use of GEM gene chips and qPCR. Our findings also demonstrate that certain methodological approaches are less useful in attempting to assess the magnitude of sex-associated differences in the lacrimal gland. These results support our hypothesis that sex-related differences in gene expression play a role in the sexual dimorphism of the lacrimal gland.


Assuntos
Regulação da Expressão Gênica , Aparelho Lacrimal/metabolismo , Animais , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Caracteres Sexuais , Transcrição Gênica
16.
Invest Ophthalmol Vis Sci ; 47(1): 158-68, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16384958

RESUMO

PURPOSE: The hypothesis tested in the study was that the effect of estrogen and progesterone on the lacrimal gland is mediated through specific receptors and that hormonal effects involve the regulation of gene expression and protein synthesis. METHODS: Lacrimal glands were collected from young adult, ovariectomized mice, that were treated with 17beta-estradiol, progesterone, 17beta-estradiol plus progesterone or vehicle for 2 weeks. Glands were pooled according to treatment, processed for the isolation of RNA, and evaluated for differentially expressed mRNAs by using gene microarrays. Bioarray data were analyzed with sophisticated bioinformatics and statistical programs. The expression of selected genes was verified by using gene chips and quantitative real-time PCR methods. RESULTS: The results demonstrate that 17beta-estradiol, progesterone, or both hormones together significantly influences the expression of hundreds of genes in the mouse lacrimal gland. Sex steroid treatment led to numerous alterations in gene activities related to transcriptional control, cell growth and/or maintenance, cell communication, signal transduction, enzyme catalysis, immune expression, and the binding and metabolism of nucleic acids and proteins. A number of the 17beta-estradiol, progesterone or 17beta-estradiol plus progesterone effects on gene expression were similar, but most were unique to each treatment. Of particular interest was the finding that these hormones seem to contribute little to the known sex-related differences in gene expression of the lacrimal gland. CONCLUSIONS: These results support the hypothesis that estrogen's and progesterone's action on the lacrimal gland involves the regulation of numerous genes. However, these hormone effects do not appear to represent a major factor underlying the sexual dimorphism of gene expression in lacrimal tissue.


Assuntos
Estradiol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Aparelho Lacrimal/metabolismo , Progesterona/farmacologia , Animais , Combinação de Medicamentos , Proteínas do Olho/genética , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Ovariectomia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Invest Ophthalmol Vis Sci ; 46(10): 3666-75, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16186348

RESUMO

PURPOSE: In prior work, it has been found that the meibomian gland is an androgen target organ, that androgens modulate lipid production within this tissue, and that androgen deficiency is associated with glandular dysfunction and evaporative dry eye. This study's purpose was to test the hypothesis that the androgen control of the meibomian gland involves the regulation of gene expression. METHODS: Meibomian glands were obtained from orchiectomized mice that were treated with placebo or testosterone for 14 days. Tissues were processed for the analysis of differentially expressed mRNAs by using gene bioarrays, gene chips, and real-time PCR procedures. Bioarray data were analyzed with GeneSifter software (VizX Labs LLC, Seattle, WA). RESULTS: The results show that testosterone influenced the expression of more than 1590 genes in the mouse meibomian gland. This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin B), and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A). Some of the most significant androgen effects were directed toward stimulation of genes associated with lipid metabolism, sterol biosynthesis, fatty acid metabolism, protein transport, oxidoreductase activity, and peroxisomes. CONCLUSIONS: These findings demonstrate that testosterone regulates the expression of numerous genes in the mouse meibomian gland and that many of these genes are involved in lipid metabolic pathways.


Assuntos
Proteínas do Olho/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glândulas Tarsais/metabolismo , Testosterona/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sequência com Séries de Oligonucleotídeos , Orquiectomia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
18.
J Steroid Biochem Mol Biol ; 96(5): 401-13, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16006120

RESUMO

The objective of this study was to determine the nature and extent of androgen influence on gene expression in the lacrimal gland. Lacrimal glands were obtained from orchiectomized mice that had been treated with testosterone or vehicle for 2 weeks, as well as from testicular feminized mice and their Tabby controls. Samples were pooled according to experiment, processed for the isolation of RNA, and analyzed for differentially expressed mRNAs by using primarily CodeLink Bioarrays, GEM 1 and 2 gene chips and quantitative real-time PCR (qPCR) procedures. Gene chip data were analyzed with GeneSifter.Net software. Our results demonstrate that testosterone regulates the expression of over 2000 genes in the lacrimal gland. Gene ontologies most affected by androgen treatment included those related to cell growth, proliferation and metabolism, cell communication and transport, nucleic acid binding, signal transduction and receptor activities. Our findings also indicate that androgen action may be mediated, at least in part, through classical androgen receptors, and may contribute to the sex-related differences in gene expression of lacrimal tissue. Overall, these results support our working hypothesis that androgen action on the lacrimal gland is mediated primarily through a receptor-associated regulation of gene transcription.


Assuntos
Androgênios/fisiologia , Regulação da Expressão Gênica/fisiologia , Aparelho Lacrimal/fisiologia , Animais , Regulação para Baixo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Orquiectomia , RNA Mensageiro/metabolismo , Caracteres Sexuais , Testosterona/fisiologia , Regulação para Cima
19.
J Cataract Refract Surg ; 31(11): 2093-100, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16412921

RESUMO

PURPOSE: To evaluate the safety and efficacy of laser in situ keratomileusis (LASIK) to enhance refractive status following other corneal surgical procedures. SETTING: Clinical office-based practice. METHODS: Seventy-one eyes of 57 patients had LASIK for refractive errors following radial keratotomy (n = 22), astigmatic keratotomy (n = 13), photorefractive keratectomy (n = 18), and penetrating keratoplasty (n = 18). A Moria LSK-1 microkeratome was used with a Visx S2 or Wavelight Allegretto excimer laser. Data were acquired by retrospective chart review of all appropriately qualified patients. RESULTS: The mean preoperative manifest refractive spherical equivalent (MRSE) was -3.93 diopters (D) +/- 2.83 (SD) in myopic eyes and +1.43 +/- 1.79 D in hyperopic eyes. The mean time from the initial corneal surgical procedure to LASIK was 65.0 months. The mean post-LASIK follow-up was 9.40 months (range 1 to 42 months). Postoperatively, the mean MRSE was -0.85 +/- 1.42 D in myopic eyes (P<.0001) and -0.16 +/- 1.09 D in hyperopic eyes (P<.0001). Enhancement by LASIK was required in 14% of eyes. CONCLUSION: In eyes that have had a variety of previous corneal surgeries, LASIK offers a safe and predictable method for enhancing refractive results.


Assuntos
Astigmatismo/cirurgia , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Ceratoplastia Penetrante/efeitos adversos , Ceratotomia Radial/efeitos adversos , Ceratectomia Fotorrefrativa/efeitos adversos , Procedimentos Cirúrgicos Refrativos , Doenças da Córnea/cirurgia , Humanos , Lasers de Excimer , Erros de Refração/etiologia , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Acuidade Visual
20.
Ann N Y Acad Sci ; 966: 211-22, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12114274

RESUMO

OBJECTIVE: We have recently discovered that women with primary and secondary Sjögren's syndrome are androgen-deficient. We hypothesize that this hormone insufficiency contributes to the meibomian gland dysfunction, tear film instability, and evaporative dry eye that are characteristic of this autoimmune disorder. If our hypothesis is correct, we predict: (1) that androgens regulate meibomian gland function, control the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer; and (2) that androgen deficiency, due to an attenuation in androgen synthesis (e.g., during Sjögren's syndrome, menopause, aging, complete androgen-insensitivity syndrome [CAIS] and anti-androgen use), will lead to meibomian gland dysfunction and evaporative dry eye. The following studies were designed to test these predictions. METHODS: Experimental procedures included clinical studies, animal models, and histological, biochemical, molecular biological, and biomedical engineering techniques. RESULTS: Our results demonstrate that: (1) androgens regulate the meibomian gland. This tissue contains androgen receptor mRNA, androgen receptor protein within acinar epithelial cell nuclei, and Types 1 and 2 5alpha-reductase mRNAs. Moreover, androgens appear to modulate lipid production and gene expression in mouse and/or rabbit meibomian glands; and (2) androgen deficiency may lead to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, tear film instability, and evaporative dry eye. Thus, we have found that anti-androgen therapy in men is associated with meibomian gland disease, a decreased tear film breakup time, and functional dry eye. Furthermore, we have discovered that androgen receptor dysfunction in women with CAIS is associated with meibomian gland changes and a significant increase in the signs and symptoms of dry eye. Of interest, we have also found that androgen deficiency is associated with significant and striking alterations in the neutral and polar lipid patterns of human meibomian gland secretions. CONCLUSIONS: Our findings show that the meibomian gland is an androgen target organ and that androgen deficiency may promote meibomian gland dysfunction and evaporative dry eye. Overall, these results support our hypothesis that androgen deficiency may be an important etiologic factor in the pathogenesis of evaporative dry eye in women with Sjögren's syndrome.


Assuntos
Androgênios/deficiência , Síndromes do Olho Seco/fisiopatologia , Glândulas Tarsais/fisiopatologia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/biossíntese , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Envelhecimento/fisiologia , Androgênios/fisiologia , Animais , Doenças Autoimunes/complicações , Doenças Autoimunes/fisiopatologia , Fenômenos Químicos , Físico-Química , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/etiologia , Indução Enzimática , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Camundongos , Pós-Menopausa/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Coelhos , Receptores Androgênicos/biossíntese , Receptores Androgênicos/genética , Receptores Androgênicos/fisiologia , Caracteres Sexuais , Síndrome de Sjogren/complicações , Síndrome de Sjogren/fisiopatologia , Lágrimas/química , Testosterona/farmacologia , Testosterona/uso terapêutico , Molhabilidade
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