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1.
Taiwan J Ophthalmol ; 13(2): 242-244, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484608

RESUMO

Here, we report a case of bilateral cystoid macular edema (CME) in a woman with phakic eyes after 22 years of latanoprost use. Optical coherence tomography revealed multiple intraretinal cysts, and fluorescein angiography revealed characteristic petaloid dye leakage from the perifoveal capillaries. A cause-effect relationship was suspected when CME resolved after switching from latanoprost to dorzolamide, as confirmed by positive rechallenge and dechallenge tests. Since prostaglandin analog-induced CME has only been reported in patients with pseudophakic, aphakic, or phakic eyes with retinal conditions predisposing to macular edema, this seems to be the first reported case of latanoprost-induced CME in a patient with phakic eyes without retinal risk factors.

2.
J Glaucoma ; 28(6): 519-528, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30789526

RESUMO

PRéCIS:: Disc tilt is a characteristic of high myopia and related to lower wedge-shaped retinal nerve fiber layer (RNFL) defects in normal-tension glaucoma (NTG). In primary open-angle glaucoma (POAG), the direction of disc torsion corresponds to the location of wedge-shaped RNFL defects. PURPOSE: To evaluate the disc characteristics in high myopia and the relationships between disc tilt and torsion and the location of wedge-shaped RNFL defects in primary POAG and NTG. MATERIALS AND METHODS: The differences in disc properties and clinical characteristics between POAG (n=53) and NTG (n=82), and between high myopic (<-6 D, n=77) and non-high myopic (≥-6 D, n=58) glaucoma, were investigated. The association between disc tilt and torsion and the location of wedge-shaped RNFL defects in POAG and NTG were assessed by univariate and multivariate logistic regression analyses. RESULTS: In NTG, but not in POAG, high myopia eyes had significantly smaller discs, a lower tilt ratio (0.73±0.09), and more disc tilt (56.5%) than did non-high myopia eyes (0.80±0.09, 33.3%). In POAG, eyes with lower wedge-shaped RNFL defects had a significantly smaller torsion angle (-5.44±19.62 degrees, inferior disc torsion) than did eyes with upper defects (9.70±23.62 degrees, superior disc torsion; P=0.014). In NTG, a significantly decreased tilt ratio (0.74±0.93; P=0.001) and more disc tilt (55.9%, P=0.005) were found in eyes with lower wedge-shaped RNFL defects than in eyes with upper defects (0.81±0.09; 21.7%). The torsion degree and tilt ratio were the only factors associated with the location of wedge-shaped RNFL defects in POAG and NTG, respectively. CONCLUSIONS: In NTG, smaller and tilted discs were the characteristics of high myopia. Disc tilt was associated with lower wedge-shaped RNFL defects. In POAG, the direction of disc torsion corresponded to the location of the wedge-shaped RNFL defects.


Assuntos
Glaucoma de Ângulo Aberto/patologia , Glaucoma de Baixa Tensão/patologia , Miopia/diagnóstico , Miopia/patologia , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Adulto , Progressão da Doença , Feminino , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular , Glaucoma de Baixa Tensão/complicações , Glaucoma de Baixa Tensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Miopia/complicações , Disco Óptico/diagnóstico por imagem , Doenças do Nervo Óptico/complicações , Doenças do Nervo Óptico/patologia , Estudos Prospectivos , Campos Visuais , Adulto Jovem
3.
Int Ophthalmol ; 38(6): 2639-2648, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29063980

RESUMO

PURPOSE: To report two cases of ciliochoroidal effusion after the usage of topiramate. CASES: Two middle-aged women experienced sudden onset of acute glaucoma and acquired myopia after taking topiramate. Ultrasound biomicroscopy demonstrated bilateral ciliochoroidal effusion and angle closure. The A-scan ultrasonography revealed shallow anterior chamber and thick lens. After the treatment and drug withdrawal, intraocular pressure, refractive status and angle anatomy returned to normal and there was resolution of ciliochoroidal effusion. During the clinical course, the anterior chamber depth (ACD) increased from 2.02 to 3.30 mm (1.28 mm of changes) OD and from 1.94 to 3.36 mm (1.42 mm of changes) OS. The lens thickness (LT) became thinner from 4.53 to 4.31 mm (0.22 mm of changes) OD and from 4.59 to 4.30 mm (0.29 mm of changes) OS in the first case. In the second case, the ACD increased from 2.33 to 3.07 mm (0.74 mm of changes) OD and from 2.30 to 3.05 mm (0.75 mm of changes) OS. The LT became thinner from 4.42 to 4.27 mm (0.15 mm of changes) OD and from 4.38 to 4.26 mm (0.12 mm of changes) OS. The forward displacement of the lens-iris diaphragm contributed more to the shallowness of the anterior chamber than the thickening of the lens itself (only accounting for 20%). CONCLUSION: Topiramate-induced bilateral acute angle closure glaucoma and myopic shift was due to ciliochoroidal effusion which resulted in thicker lens and shallow anterior chamber. The later was mainly due to anterior displacement of the lens-iris diaphragm.


Assuntos
Anticonvulsivantes/efeitos adversos , Doenças da Coroide/induzido quimicamente , Glaucoma de Ângulo Fechado/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Miopia/induzido quimicamente , Topiramato/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
4.
Invest Ophthalmol Vis Sci ; 57(6): 2629-36, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-27258435

RESUMO

PURPOSE: To demonstrate that a 44-amino acid peptide from pigment epithelial-derived factor (PEDF) induces the regeneration of limbal excision wound, and the regenerated limbus can act as the regeneration source for new limbal excisional injuries in rabbit model of limbal deficiency. METHODS: Half circumference partial limbal excision was followed by PEDF peptide treatment to achieve limbal wound regeneration. Three months later, a second stage half circumference partial limbal excision removed the remaining native limbal tissue followed by PEDF peptide treatment. The structure and function of the regenerated limbus were analyzed at 3 and 6 months. Conjunctivalization was analyzed by impression cytology. Immunohistochemical analysis was performed with antibodies to corneal epithelium-associated keratin 3 (K3), conjunctival epithelium-associated keratin 13 (K13), ΔNp63α, ABCG2, and BrdU. Extensive limbal excision was performed to examine the regeneration potential of the PEDF peptide. RESULTS: Total limbal stem cell deficiency occurred with severe inflammation and conjunctivalization of the limbal wound and adjacent cornea in vehicle control eyes. In PEDF peptide treated eyes, the regenerated limbus prevented fibrovascular invasion and goblet cell migration into the corneal surface. Immunohistochemical staining of the regenerated limbus showed a wide distribution of cells expressing ΔNp63α and ABCG2 as in the native limbus. BrdU labeling assay revealed the presence of slow-cycling cells in the basal layer of the regenerated limbus. The PEDF peptide can heal extensive limbal excisional wounds and sustain ocular surface integrity. CONCLUSIONS: The addition of PEDF peptide has the potential to repair limbal excisional wounds with the recovery of normal limbus-like anatomy and function. The PEDF peptide is a potential remedy for extensive limbal injury.


Assuntos
Doenças da Córnea/tratamento farmacológico , Epitélio Corneano/patologia , Proteínas do Olho/farmacologia , Limbo da Córnea/fisiologia , Fatores de Crescimento Neural/farmacologia , Regeneração/efeitos dos fármacos , Serpinas/farmacologia , Animais , Células Cultivadas , Doenças da Córnea/metabolismo , Doenças da Córnea/patologia , Modelos Animais de Doenças , Epitélio Corneano/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Coelhos
5.
J Glaucoma ; 25(6): e569-75, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26918912

RESUMO

PURPOSE: To evaluate the morphologic characteristics of optic neuropathy and its association with visual field (VF) defects in primary open-angle glaucoma (POAG) eyes with high myopia. METHODS: In this cross-sectional study, we reviewed data from 375 Taiwanese patients (375 eyes) of POAG, ages 20 to 60 years. Optic disc photographs were used for planimetric measurements of morphologic variables. The myopic refraction was divided into high myopia (<-6.0 D) and nonhigh myopia (moderate myopia to hyperopia). The optic disc area was classified as moderate (1.59 to 2.85 mm(2)), large, and small. Differences in characteristics between groups, correlations with the disc area, and factors associated with VF defects were determined. RESULTS: Of the 142 highly myopic eyes, 33 (23%) had a large disc, 26 (18%) had a small disc, and 55 (39%) had a tilted disc. Large discs had a higher cup-to-disc (C/D) area ratio and a higher tilt ratio; small discs had a smaller rim area and a lower tilt ratio (all P<0.05). Characteristics associated with high myopia included a smaller rim area, a higher C/D area ratio, and a lower tilt ratio (all P<0.001). In logistic regression, the refraction, the C/D area ratio, the rim area, and the tilt ratio (all P<0.05) were associated with VF defects. CONCLUSIONS: In Taiwanese individuals with POAG, our study found that tilted, large, or small discs were prevalent in highly myopic eyes. Of these characteristics, only the disc tilt and high myopia by itself were associated with the severity of glaucomatous optic neuropathy.


Assuntos
Glaucoma de Ângulo Aberto/complicações , Pressão Intraocular , Miopia/complicações , Disco Óptico/patologia , Doenças do Nervo Óptico/complicações , Escotoma/etiologia , Campos Visuais/fisiologia , Adulto , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/diagnóstico , Miopia/fisiopatologia , Doenças do Nervo Óptico/diagnóstico , Escotoma/diagnóstico , Escotoma/fisiopatologia , Índice de Gravidade de Doença , Tomografia de Coerência Óptica , Adulto Jovem
6.
Am J Physiol Cell Physiol ; 309(3): C159-68, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26040897

RESUMO

In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser(93)-Leu(112)) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2'-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration.


Assuntos
Proteínas do Olho/farmacologia , Músculo Esquelético/fisiologia , Fatores de Crescimento Neural/farmacologia , Regeneração/fisiologia , Serpinas/farmacologia , Células-Tronco/fisiologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Mioblastos/fisiologia , Ratos , Ratos Sprague-Dawley , Regeneração/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos
7.
Invest Ophthalmol Vis Sci ; 56(4): 2126-34, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25678686

RESUMO

PURPOSE: To investigate the potential of a pigment epithelial-derived factor (PEDF) peptide 44-mer to promote limbal regeneration in a rabbit partial limbal deficiency model. METHODS: Limbal excision (180°) was created surgically, and topical application of 44-mer-containing ointment once a day for 2 weeks was started immediately after injury. Limbal barrier function was inspected at 2 and 6 months after treatment. Corneal neovascularization was observed under slit-lamp microscope. The presence of goblet cells on the corneal surface was examined using impression cytology. The resulting repair tissue was assessed by immunohistochemical staining with antibodies for putative limbal stem cell (LSC) markers ΔNp63α and ABCG2. Cells harvested from the regenerated tissue were analyzed for colony-forming capacity and expression of LSC markers by immunostaining assay and quantitative real-time PCR (qPCR). RESULTS: Eyes treated with the 44-mer blocked vascularization and goblet cell migration onto the corneal surface. By means of immunohistochemical staining and cell isolation in the repair tissue, we showed that LSCs were widely distributed at the regenerated tissue after 44-mer treatment. The repaired limbus contributed robustly to corneal wound healing as effectively as undamaged limbus. CONCLUSIONS: We demonstrated that 44-mer regenerates a functional limbus-like structure on limbal excision wounds. Our finding suggests that the PEDF peptide derivative may be an innovative strategy for tissue engineering and repair therapy in partial LSC deficiency diseases.


Assuntos
Lesões da Córnea/genética , Proteínas do Olho/genética , Regulação da Expressão Gênica , Limbo da Córnea/fisiologia , Fatores de Crescimento Neural/genética , RNA/genética , Regeneração , Serpinas/genética , Animais , Células Cultivadas , Lesões da Córnea/metabolismo , Lesões da Córnea/patologia , Modelos Animais de Doenças , Proteínas do Olho/biossíntese , Immunoblotting , Fatores de Crescimento Neural/biossíntese , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Serpinas/biossíntese
8.
Stem Cells ; 31(9): 1775-84, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23553951

RESUMO

Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63α, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ΔNp63α-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78-121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ΔNp63α-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound.


Assuntos
Epitélio Corneano/patologia , Proteínas do Olho/farmacologia , Limbo da Córnea/citologia , Fatores de Crescimento Neural/farmacologia , Serpinas/farmacologia , Células-Tronco/citologia , Cicatrização/efeitos dos fármacos , Animais , Bromodesoxiuridina/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Epitélio Corneano/efeitos dos fármacos , Imunofluorescência , Humanos , Camundongos , Mitógenos/farmacologia , Células NIH 3T3 , Peptídeos/farmacologia , Coelhos , Fator de Transcrição STAT3/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Ophthalmology ; 120(3): 544-552, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23207174

RESUMO

PURPOSE: To evaluate the clinical features of peripapillary choroidal cavitation (PCC) detected by optical coherence tomography (OCT). DESIGN: Retrospective, observational case series. PARTICIPANTS: One hundred twenty-two eyes from 83 patients diagnosed with PCC by OCT database review were included in this study. METHODS: Stereoscopic color fundus photographs from eyes with PCC were reviewed by 2 independent ophthalmologists. They were masked to the refractive error, axial length, and OCT findings. MAIN OUTCOME MEASURES: Chart review and data analysis included gender, age, best-corrected visual acuity (BCVA), refractive error, axial length, clinical appearance of the peripapillary area, and associated funduscopic abnormalities. RESULTS: One hundred twenty-two eyes with PCC from 83 patients were analyzed. Among the patients, 41.8% were men and 58.2% were women. The mean age was 48.2 ± 12.6 years and mean BCVA in logarithm of the minimum angle of resolution units was 0.23 ± 0.43. The mean refractive error in spherical equivalent was -9.03 ± 5.11 diopters (D) and mean axial length (AL) was 27.36 ± 2.09 mm. With respect to refractive error, 90 eyes (73.8%) were highly myopic (≥-6.00 D), 24 eyes (19.7%) had low myopia (<-6.00 D), 5 eyes (4.1%) were emmetropic (1.00 to -1.00 D), and 3 eyes (2.6%) were hyperopic (>1.00 D). Forty eyes (32.8%) with PCC had AL of less than 26.50 mm (mean, 25.11 ± 1.07 mm; range, 22.51-26.42 mm). Patients with eyes with PCC that had low myopia, were emmetropic, and were hyperopic also were significantly older than patients with highly myopic eyes (P<0.05). Stereoscopic fundus photographs demonstrated a yellow-orange, localized, well-circumscribed peripapillary lesion in 57 (46.7%) eyes with PCC. A PCC with opening was observed in 14 (26.4%) of 53 eyes with excavated myopic conus and in 5 (7.2%) of 69 eyes without excavated myopic conus (P<0.05). CONCLUSIONS: This study demonstrated that peripapillary choroidal cavitation is common and not exclusive to highly myopic eyes. The funduscopic finding of a yellow-orange peripapillary abnormality may not be evident in all eyes with demonstrable PCC by OCT. Although its pathogenesis and pathologic significance require further investigation, PCC may be a degenerative change in aging eyes.


Assuntos
Doenças da Coroide/diagnóstico , Tomografia de Coerência Óptica , Adulto , Idoso , Comprimento Axial do Olho/fisiopatologia , Doenças da Coroide/etiologia , Doenças da Coroide/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/complicações , Disco Óptico , Erros de Refração/fisiopatologia , Estudos Retrospectivos , Acuidade Visual/fisiologia , Adulto Jovem
10.
J Biol Chem ; 286(41): 35943-35954, 2011 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-21846721

RESUMO

Pigment epithelium-derived factor (PEDF) is an intrinsic anti-angiogenic factor and a potential anti-tumor agent. The tumoricidal mechanism of PEDF, however, has not been fully elucidated. Here we report that PEDF induces the apoptosis of TC-1 and SK-Hep-1 tumor cells when they are cocultured with bone marrow-derived macrophages (BMDMs). This macrophage-mediated tumor killing is prevented by blockage of TNF-related apoptosis-inducing ligand (TRAIL) following treatment with the soluble TRAIL receptor. PEDF also increases the amount of membrane-bound TRAIL on cultured mouse BMDMs and on macrophages surrounding subcutaneous tumors. PEDF-induced tumor killing and TRAIL induction are abrogated by peroxisome proliferator-activated receptor γ (PPARγ) antagonists or small interfering RNAs targeting PPARγ. PEDF also induces PPARγ in BMDMs. Furthermore, the activity of the TRAIL promoter in human macrophages is increased by PEDF stimulation. Chromatin immunoprecipitation and DNA pull-down assays confirmed that endogenous PPARγ binds to a functional PPAR-response element (PPRE) in the TRAIL promoter, and mutation of this PPRE abolishes the binding of the PPARγ-RXRα heterodimer. Also, PPARγ-dependent transactivation and PPARγ-RXRα binding to this PPRE are prevented by PPARγ antagonists. Our results provide a novel mechanism for the tumoricidal activity of PEDF, which involves tumor cell killing via PPARγ-mediated TRAIL induction in macrophages.


Assuntos
Apoptose , Proteínas do Olho/metabolismo , Macrófagos/metabolismo , Neoplasias/metabolismo , Fatores de Crescimento Neural/metabolismo , Serpinas/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Animais , Linhagem Celular Transformada , Linhagem Celular Tumoral , Técnicas de Cocultura , Proteínas do Olho/imunologia , Humanos , Macrófagos/imunologia , Camundongos , Mutação , Neoplasias/imunologia , Fatores de Crescimento Neural/imunologia , PPAR gama/imunologia , PPAR gama/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Elementos de Resposta/imunologia , Receptor X Retinoide alfa/imunologia , Receptor X Retinoide alfa/metabolismo , Serpinas/imunologia , Ligante Indutor de Apoptose Relacionado a TNF/imunologia
11.
J Glaucoma ; 20(2): 126-32, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20436367

RESUMO

PURPOSE: To compare Humphrey Matrix (Matrix) with Octopus perimetry for assessing visual field (VF) indices, size, severity, and location in the glaucomatous VF defect. METHODS: Matrix (30-2 threshold program) and Octopus 1-2-3 perimetry (G1X program) were conducted on 60 eyes of 60 patients with primary open-angle glaucoma. The VF indices derived by Matrix (mean deviation, pattern standard deviation), and Octopus (mean defect, square root of loss variance, corrected loss variance) were compared, as were the size (percentage of points depressed < 5% or < 1%) and the severity (score and Hodapp-Parrish-Anderson grade) of the VF defect. RESULTS: Matrix and Octopus results agreed well overall for VF indices, size, severity, and locations of the VF defect. The mean deviation and pattern standard deviation in Matrix were significantly higher than the mean defect, square root of loss variance and square root of corrected loss variance in Octopus. On the total deviation plot, the size of the VF defect in the superior and nasal fields reported by Matrix was significantly higher than by Octopus. The VF defect score by Matrix was significantly higher than that by Octopus in the superior, nasal, and whole fields. More eyes had a worse grade by Matrix than by Octopus. CONCLUSIONS: Matrix compared well with Octopus in detecting glaucomatous visual field defects. However, the defects reported by Matrix were larger and more severe than with Octopus.


Assuntos
Glaucoma de Ângulo Aberto/diagnóstico , Transtornos da Visão/diagnóstico , Testes de Campo Visual/instrumentação , Campos Visuais , Adulto , Idoso , Feminino , Gonioscopia , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
12.
J Glaucoma ; 19(7): 483-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19855298

RESUMO

PURPOSE: To analyze the clinical characteristics and prognostic significance of disc hemorrhage in primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and primary angle-closure glaucoma (PACG). METHODS: Records of patients with POAG, NTG, or PACG and a history of disc hemorrhage were collected for this retrospective, observational cohort study. RESULTS: Of 1134 patients with POAG, 513 with NTG and 770 with PACG, 63 (5.6%), 36 (7.0%), and 44 (5.7%), respectively, had disc hemorrhage over a mean of 9 years of follow-up. There were no significant differences in the laterality, episodes, duration of hemorrhage, and frequency of recurrent hemorrhage among the 3 types. The intraocular pressure and cup-to-disc ratio did not differ significantly between eyes with and fellow eyes without hemorrhage. There was a significant association between disc hemorrhage and visual field progression [odds ratio: 2.78 (P = 0.004), 3.75 (P = 0.040), and 4.50 (P = 0.011) for POAG, NTG, and PACG, respectively]. CONCLUSIONS: Normal tension glaucoma has the highest incidence of disc hemorrhage, followed by PACG and POAG, which have similar incidence. The clinical characteristics of hemorrhage are not different among 3 types of glaucoma. The presence of disc hemorrhage is associated with the progression of glaucomatous optic neuropathy and visual field defects in POAG, NTG, and PACG.


Assuntos
Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Baixa Tensão/diagnóstico , Disco Óptico/patologia , Hemorragia Retiniana/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Gonioscopia , Humanos , Pressão Intraocular , Glaucoma de Baixa Tensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Hemorragia Retiniana/fisiopatologia , Estudos Retrospectivos , Tonometria Ocular , Acuidade Visual , Testes de Campo Visual
13.
Jpn J Ophthalmol ; 53(4): 380-3, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19763755

RESUMO

BACKGROUND: We describe progressive optic neuropathy after recurrent disc hemorrhages in patients with primary angle-closure glaucoma. CASES: Three Taiwanese Chinese patients with primary angle-closure glaucoma and recurrent disc hemorrhages were followed for 10 years. OBSERVATIONS: Despite good control of intraocular pressure, progressive enlargement of optic disc cupping and visual field defects corresponding to the location of disc hemorrhages were noted after recurrent hemorrhages. CONCLUSIONS: Disc hemorrhages are not particularly rare in primary angle-closure glaucoma and may be a sign of a poor prognosis.


Assuntos
Glaucoma de Ângulo Fechado/fisiopatologia , Disco Óptico/fisiopatologia , Doenças do Nervo Óptico/fisiopatologia , Hemorragia Retiniana/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Pressão Intraocular , Masculino , Prognóstico , Recidiva , Escotoma/fisiopatologia , Testes de Campo Visual , Campos Visuais
14.
Am J Physiol Cell Physiol ; 296(2): C273-84, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19091957

RESUMO

Pigment epithelium-derived factor (PEDF) is an intrinsic antiangiogenic factor and a potential therapeutic agent. Previously, we discovered the mechanism of PEDF-induced apoptosis of human umbilical vein endothelial cells (HUVECs) as sequential induction/activation of p38 mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor gamma (PPAR-gamma), and p53. In the present study, we investigated the signaling role of cytosolic calcium-dependent phospholipase A(2)-alpha (cPLA(2)-alpha) to bridge p38 MAPK and PPAR-gamma activation. PEDF induced cPLA(2)-alpha activation in HUVECs and in endothelial cells in chemical burn-induced vessels on mouse cornea. The cPLA(2)-alpha activation is evident from the phosphorylation and nuclear translocation of cPLA(2)-alpha as well as arachidonic acid release and the cleavage of PED6, a synthetic PLA(2) substrate. Such activation can be abolished by p38 MAPK inhibitor. The PEDF-induced PPAR-gamma activation, p53 expression, caspase-3 activity, and apoptosis can be abolished by both cPLA(2) inhibitor and small interfering RNA targeting cPLA(2)-alpha. Our observation not only establishes the signaling role of cPLA(2)-alpha but also for the first time demonstrates the sequential activation of p38 MAPK, cPLA(2)-alpha, PPAR-gamma, and p53 as the mechanism of PEDF-induced endothelial cell apoptosis.


Assuntos
Apoptose , Células Endoteliais/enzimologia , Células Endoteliais/patologia , Proteínas do Olho/metabolismo , Fosfolipases A2 do Grupo IV/metabolismo , Fatores de Crescimento Neural/metabolismo , Serpinas/metabolismo , Transdução de Sinais , Transporte Ativo do Núcleo Celular , Animais , Apoptose/efeitos dos fármacos , Ácido Araquidônico/metabolismo , Queimaduras Químicas/enzimologia , Queimaduras Químicas/patologia , Caspase 3/metabolismo , Células Cultivadas , Neovascularização da Córnea/enzimologia , Neovascularização da Córnea/patologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/enzimologia , Queimaduras Oculares/patologia , Proteínas do Olho/administração & dosagem , Fosfolipases A2 do Grupo IV/antagonistas & inibidores , Fosfolipases A2 do Grupo IV/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Crescimento Neural/administração & dosagem , PPAR gama/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Proteínas Recombinantes/metabolismo , Serina , Serpinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
J Biol Chem ; 283(44): 30273-88, 2008 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-18718914

RESUMO

15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a potent anti-angiogenic factor and induces endothelial cell apoptosis, although the mechanism remains unclear. In this study, 15d-PGJ(2) was found to increase p53 levels of the human umbilical vein endothelial cells by stabilizing p53. Both 15d-PGJ(2)-induced apoptosis and the induction of p21(Waf1) and Bax can be abolished by p53 small interfering RNA but not by peroxisome proliferator-activated receptor gamma inhibitors. Moreover, 15d-PGJ(2) activated JNK and p38 MAPK while inducing p53 phosphorylation at sites responsible for p53 activity. JNK inhibitor (SP600125) or p38 MAPK inhibitor (SB203580) pretreatment attenuated 15d-PGJ(2)-mediated apoptosis and suppressed the p21(Waf1) and Bax expressions without affecting p53 protein accumulation. Pretreatment with SP600125 partially prevented the phosphorylation of p53 at serines 33 and 392 induced by 15d-PGJ(2). 15d-PGJ(2) was also found to induce reactive oxygen species generation and partially blocked nuclear factor-kappaB activity. Pretreatment with antioxidant N-acetylcysteine prevented the p53 accumulation, the phosphorylations of JNK and p38 MAPK, the inhibition of NF-kappaB activity, as well as the apoptosis induced by 15d-PGJ(2). Using a mouse model of corneal neovascularization, it was demonstrated in vivo that 15d-PGJ(2) induced reactive oxygen species generation, activated JNK and p38 MAPK, induced p53 accumulation/phosphorylation, and induced vascular endothelial cell apoptosis, which could be abolished by N-acetylcysteine, SP600125, SB203580, or a virus-derived amphipathic peptides-based p53 small interfering RNA. This is the first study that 15d-PGJ(2) induces vascular endothelial cell apoptosis through the signaling of JNK and p38 MAPK-mediated p53 activation both in vitro and in vivo, further establishing the potential of 15d-PGJ(2) as an anti-angiogenesis agent.


Assuntos
Apoptose , Endotélio Vascular/citologia , Sistema de Sinalização das MAP Quinases , Prostaglandina D2/análogos & derivados , Proteína Supressora de Tumor p53/metabolismo , Animais , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Ativação Enzimática , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Biológicos , NF-kappa B/metabolismo , Fosforilação , Prostaglandina D2/metabolismo , Prostaglandina D2/fisiologia , Espécies Reativas de Oxigênio
16.
Ophthalmology ; 115(8): 1328-33, 1333.e1, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18187197

RESUMO

PURPOSE: To analyze the characteristics of disc hemorrhage in primary angle-closure glaucoma (PACG). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Patients seen in glaucoma clinics with PACG and a history of disc hemorrhage. METHODS: Goldmann tonometry, gonioscopy, ophthalmoscopy, and automated perimetry. MAIN OUTCOME MEASURES: Location, number of episodes, and duration of disc hemorrhage; comparison of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in eyes with and fellow eyes without hemorrhage; and changes of CDR and visual fields (VFs) on follow-up. RESULTS: The mean duration of follow-up was 109.2+/-63 months (range, 7-261). Of 770 patients with PACG, 44 (5.7%) had disc hemorrhage at some point in their history, of whom 30 (68%) had unilateral and 14 (32%) had bilateral hemorrhages, either alternately or simultaneously in both eyes. There were a total of 111 hemorrhages in 58 eyes, including 23 eyes (40%) with recurrent hemorrhages. Of the 111 total hemorrhages, 85 (77%) occurred in the inferotemporal and 19 (17%) in the superotemporal sector of the disc. Among 23 eyes with recurrent disc hemorrhages, 11 (48%) had recurrence in the same sector of the disc. The average duration of hemorrhages was 12.8+/-8.1 weeks. The IOP and CDR did not differ significantly between eyes with and fellow eyes without hemorrhage. For patients with unilateral disc hemorrhage, progressive changes in the CDR were found in both the eyes with and fellow eyes without disc hemorrhage, but VF defects worsened only in eyes with disc hemorrhage. CONCLUSIONS: The incidence of disc hemorrhage in patients with PACG was 5.7% over 9 years of follow-up. Despite its relative infrequency, disc hemorrhage in PACG was associated with progression of glaucomatous optic neuropathy and VF defects.


Assuntos
Glaucoma de Ângulo Fechado/diagnóstico , Disco Óptico/patologia , Hemorragia Retiniana/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Glaucoma de Ângulo Fechado/fisiopatologia , Gonioscopia , Humanos , Incidência , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Doenças do Nervo Óptico/fisiopatologia , Hemorragia Retiniana/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Tonometria Ocular , Transtornos da Visão/fisiopatologia , Testes de Campo Visual , Campos Visuais
17.
Ophthalmologica ; 221(6): 388-94, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17947825

RESUMO

AIM: To evaluate the biometric difference between eyes with acute angle-closure (AAC) attack, their uninvolved fellow eyes and eyes with chronic angle-closure glaucoma (CACG). METHODS: Patients with prior laser iridotomy on both eyes for unilateral AAC attack or CACG were recruited. We compared ocular biometric parameters by A-scan ultrasonography of the acutely affected eyes with those of the uninvolved fellow eyes and with eyes affected by CACG. RESULTS: Thirty-three patients with unilateral AAC attack and 41 patients with CACG were included. The eyes with AAC attack had a significantly shallower anterior chamber depth (ACD), thicker lens, shorter axial length, higher lens/axial length factor and more anteriorly positioned lens than the eyes with CACG. The uninvolved fellow eyes had a significantly shallower ACD, shorter axial length and higher lens/axial length factor compared with the eyes with CACG. Acutely affected eyes had a shallower ACD and more anteriorly positioned lens than did the uninvolved fellow eyes. CONCLUSION: Eyes with AAC attack had a more crowded anterior segment compared with uninvolved fellow eyes and those affected by CACG. In addition to ACD, relative lens size, represented by the lens/axial length factor, and relative lens position appear to play important roles in the development of AAC attack.


Assuntos
Olho/diagnóstico por imagem , Glaucoma de Ângulo Fechado/diagnóstico por imagem , Doença Aguda , Idoso , Câmara Anterior/diagnóstico por imagem , Doença Crônica , Feminino , Glaucoma de Ângulo Fechado/cirurgia , Humanos , Iris/cirurgia , Cristalino/diagnóstico por imagem , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos , Ultrassonografia
18.
J Formos Med Assoc ; 102(3): 183-8, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12783136

RESUMO

BACKGROUND AND PURPOSE: Primary angle-closure glaucoma (PACG) is the predominant form of glaucoma among Asians. Although numerous studies have been done to describe the characteristic optic disc changes in patients with primary open angle glaucoma (POAG) which is the predominant form of glaucoma among Western populations, few studies have evaluated the optic disc changes in patients with PACG. The aim of this study was to elucidate the characteristic intrapapillary and parapapillary disc changes in PACG in a cross-sectional study and to develop a practical approach to the detection of glaucomatous optic disc changes in PACG by ophthalmoscopic examination. METHODS: A total of 103 eyes in 103 PACG patients were studied. Forty one eyes of 41 age- and sex-matched healthy subjects served as controls. Three glaucoma-trained subspecialists examined stereophotographs of optic discs to evaluate the intrapapillary and parapapillary changes. The differences in PACG and control group eyes were compared. RESULTS: Concentric steep enlargement of the optic disc was found in 99 PACG eyes (96%). Local notching was noted in only 3 eyes, and vertically oval-shaped cupping of the optic disc in only 1 eye. Disc hemorrhage was not detected in any eye. Parapapillary atrophy of the alpha zone involving both temporal and nasal side of the optic disc and parapapillary atrophy of beta zone were significantly more frequent in the PACG group. The presence of an alpha zone or a beta zone simultaneously involving both the temporal and nasal side of the optic disc was associated with more severe optic nerve head damage. CONCLUSIONS: The intrapapillary change in the PACG group eyes reflected the development of cupping in PACG patients with small and compact optic discs. The parapapillary atrophy paralleled the intrapapillary optic disc cupping in eyes of the PACG group.


Assuntos
Glaucoma de Ângulo Fechado/patologia , Atrofia Óptica/patologia , Disco Óptico/patologia , Estudos de Casos e Controles , Feminino , Glaucoma de Ângulo Fechado/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Óptica/etiologia , Taiwan
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