Publications (7)8.01 Total impact
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Article: EXPRESSION OF SIRT1 IN CHOROIDAL NEOVASCULAR MEMBRANES.
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ABSTRACT: PURPOSE:: SIRT1 is a deacetylase that has been shown to be instrumental in embryonic and pathologic vascular formation. The purpose of this study was to evaluate the potential role of SIRT1 in the pathogenesis of choroidal neovascularization in age-related macular degeneration. METHODS:: The expression of SIRT1 was assessed via immunohistochemistry in nine excised human choroidal neovascularization membranes and seven non-age-related macular degeneration donor eyes. Enzyme-linked immunosorbent assay-based angiogenesis arrays were used to assess the potential of an SIRT1 inhibitor, nicotinamide, to reduce secretion of 10 unique proangiogenic cytokines from retinal pigment epithelial cells. RESULTS:: SIRT1 was expressed more frequently in choroidal neovascularization membranes than donor eyes about vascular endothelial cells (78 vs. 29% positive cases) and retinal pigment epithelial cells (57 vs. 14% positive cases). SIRT1 inhibition in retinal pigment epithelial cells correlated with significantly decreased secretion of three potent proangiogenic cytokines: angiogenin, platelet-derived growth factor BB, and vascular endothelial growth factor A. CONCLUSION:: SIRT1 levels appear elevated in human choroidal neovascularization membranes compared with control eyes. Moreover, inhibition of SIRT1 activity is correlated with decreased secretion of potent proangiogenic cytokines. Collectively, these data support a potential role for SIRT1 in the pathogenesis of neovascular age-related macular degeneration.Retina (Philadelphia, Pa.) 11/2012; · 2.93 Impact Factor -
Article: The effect of blue light exposure in an ocular melanoma animal model.
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ABSTRACT: Uveal melanoma (UM) cell lines, when exposed to blue light in vitro, show a significant increase in proliferation. In order to determine if similar effects could be seen in vivo, we investigated the effect of blue light exposure in a xenograft animal model of UM. Twenty New Zealand albino rabbits were injected with 1.0 x 10(6) human UM cells (92.1) in the suprachoroidal space of the right eye. Animals were equally divided into two groups; the experimental group was exposed to blue light, while the control group was protected from blue light exposure. The eyes were enucleated after sacrifice and the proliferation rates of the re-cultured tumor cells were assessed using a Sulforhodamine-B assay. Cells were re-cultured for 1 passage only in order to maintain any in vivo cellular changes. Furthermore, Proliferating Cell Nuclear Antigen (PCNA) protein expression was used to ascertain differences in cellular proliferation between both groups in formalin-fixed, paraffin-embedded eyes (FFPE). Blue light exposure led to a statistically significant increase in proliferation for cell lines derived from intraocular tumors (p < 0.01). PCNA expression was significantly higher in the FFPE blue light treated group when compared to controls (p = 0.0096). There is an increasing amount of data suggesting that blue light exposure may influence the progression of UM. Our results support this notion and warrant further studies to evaluate the ability of blue light filtering lenses to slow disease progression in UM patients.Journal of Experimental & Clinical Cancer Research 04/2009; 28:48. · 2.15 Impact Factor -
Article: Expression of cyclooxygenase-2 in choroidal neovascular membranes from age-related macular degeneration patients.
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ABSTRACT: The objective of this study was to investigate the expression of cyclooxygenase (COX)-2 in human choroidal neovascular membranes. Paraffin-embedded sections of choroidal neovascular membranes excised from 16 patients with wet age-related macular degeneration were used for this study. Sections were subjected to immunohistochemistry using a monoclonal mouse antihuman COX-2 antibody. Staining was classified as either negative or positive in retinal pigment epithelial cells, vascular endothelial cells, and fibroblasts. Serial sections were stained for vimentin expression to confirm tissue antigenicity. Eleven of 16 (69%) choroidal neovascular membranes stained positive for COX-2 in retinal pigment epithelial cells, with 6 (38%) of these also expressing COX-2 in vascular endothelial cells and 6 (38%) in fibroblasts. None of the sections that were negative for COX-2 in the retinal pigment epithelial cells showed COX-2 expression in the other cell types assessed. There was a statistically significant difference (P = 0.0097) in the mean ages between the COX-2 positive group (65.6 years) and COX-2 negative group (76.8 years) as determined by a two-tailed, unpaired Student's t-test. The expression of COX-2 in human choroidal neovascular membranes suggests a possible role for this modulator in age-related macular degeneration pathogenesis. The age-dependent expression observed is novel and warrants further investigation.Retina (Philadelphia, Pa.) 10/2008; 29(2):176-80. · 2.93 Impact Factor -
Article: Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma
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ABSTRACT: Abstract Background Melan-A and tyrosinase are new immunohistochemical markers that can be used in the diagnosis of melanocytic lesions. The aim of this study was to investigate the correlation between radiotherapy or clinicohistopathological parameters and the expression of melan-A and tyrosinase in uveal melanoma. Methods Thirty-six enucleated cases of uveal melanoma were studied. The formalin-fixed, paraffin-embedded specimens were immunostained with monoclonal antibodies against melan-A and tyrosinase. The samples were classified as either positive or negative. The chi-square or the Student-t tests were used to test for the correlation of the expression rates of melan-A and tyrosinase with clinico-pathological parameters. Results Melan-A and tyrosinase were positive in 33 (91.7%) and 35 (97.2%) of the specimens, respectively. There was no significant association between the expression of melan-A or tyrosinase and radiotherapy or any clinico-pathological parameter. All specimens were positive for at least one of the immunohistochemical markers. Conclusion To the best of our knowledge this is the first study concluding that the expression of melanocytic markers such as melan-A and tyrosinase is not influenced by radiotherapy or any clinico-pathological parameter. Moreover, when tyrosinase and melan-A are used together, 100% of the formalin-fixed, paraffin-embedded uveal melanoma samples tested positive for one of those markers.Journal of Carcinogenesis. 01/2007; -
Article: Prostate-specific membrane antigen is undetectable in choroidal neovascular membrane.
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ABSTRACT: Choroidal neovascular membrane (CNVM) is one of the leading causes of severe visual loss and is often associated with age-related macular degeneration (AMD). Various modalities of treatment, including photocoagulation and surgery, are being considered as options, but with limited success. Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein expressed in benign and malignant prostatic tissues, in some non-prostatic tissues, and in the endothelium of tumor-associated neovasculature of non-prostatic neoplasm. Some studies have suggested that the expression of PSMA is restricted to endothelium from tumor-associated neovasculature and might be stimulated by some tumor-secreted angiogenic factors. However, no previous study demonstrating PSMA expression in non-related tumor neovasculature, such as CNVM, has been performed to date. Furthermore, demonstration of PSMA expression in CNVM in AMD patients could reveal a novel target for antineovascular therapy. The purpose of this study was to evaluate the immunohistochemical expression of PSMA in CNVM from AMD. Immunohistochemical analysis, with a standard avidin-biotin complex technique, was performed using an anti-PSMA mouse monoclonal antibody in 30 specimens of surgically excised CNVM from AMD patients. Antibody to an endothelial cell specific marker, factor VIII, was used to confirm the location of the endothelial cells. The angiogenic microvessels of the 30 cases demonstrated negative staining to PSMA while factor VIII was expressed in all cases. Seventy-five percent of the secretory-acinar epithelium of the prostatic hyperplasia specimen stained positive, confirming that the immunohistochemical technique was correctly performed. The absence of PSMA expression in non-tumoral neovasculature supports the theory, previously suggested, that endothelial cell PSMA expression may be stimulated by one or more tumor-secreted angiogenic factors. Angiogenesis is very important in neoplasia and the endothelial expression of PSMA in tumor-associated neovasculature may represent a target for antineovasculature-based therapy. The absence of PSMA expression in CNVM suggests that PSMA may not be a potential target for antineovasculature-based therapy.Journal of Carcinogenesis 02/2006; 5:21. -
Article: Clinical-histopathological correlation in a case of Coats' disease
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ABSTRACT: Abstract Background Coats' disease is a non-hereditary ocular disease, with no systemic manifestation, first described by Coats in 1908. It occurs more commonly in children and has a clear male predominance. Most patients present clinically with unilateral decreased vision, strabismus or leukocoria. The most important differential diagnosis is unilateral retinoblastoma, which occurs in the same age group and has some overlapping clinical manifestations. Case presentation A 4 year-old girl presented with a blind and painful right eye. Ocular examination revealed neovascular glaucoma, cataract and posterior synechiae. Although viewing of the fundus was impossible, computed tomography disclosed total exsudative retinal detachment in the affected eye. The eye was enucleated and subsequent histopathological evaluation confirmed the diagnosis of Coats' disease. Conclusion General pathologists usually do not have the opportunity to receive and study specimens from patients with Coats' disease. Coats' disease is one of the most important differential diagnoses of retinoblastoma. Therefore, It is crucial for the pathologist to be familiar with the histopathological features of the former, and distinguish it from the latter.Diagnostic Pathology. 01/2006; -
Article: Prostate-specific membrane antigen is undetectable in choroidal neovascular membrane
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ABSTRACT: Abstract Background Choroidal neovascular membrane (CNVM) is one of the leading causes of severe visual loss and is often associated with age-related macular degeneration (AMD). Various modalities of treatment, including photocoagulation and surgery, are being considered as options, but with limited success. Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein expressed in benign and malignant prostatic tissues, in some non-prostatic tissues, and in the endothelium of tumor-associated neovasculature of non-prostatic neoplasm. Some studies have suggested that the expression of PSMA is restricted to endothelium from tumor-associated neovasculature and might be stimulated by some tumor-secreted angiogenic factors. However, no previous study demonstrating PSMA expression in non-related tumor neovasculature, such as CNVM, has been performed to date. Furthermore, demonstration of PSMA expression in CNVM in AMD patients could reveal a novel target for antineovascular therapy. The purpose of this study was to evaluate the immunohistochemical expression of PSMA in CNVM from AMD. Methods Immunohistochemical analysis, with a standard avidin-biotin complex technique, was performed using an anti-PSMA mouse monoclonal antibody in 30 specimens of surgically excised CNVM from AMD patients. Antibody to an endothelial cell specific marker, factor VIII, was used to confirm the location of the endothelial cells. Results The angiogenic microvessels of the 30 cases demonstrated negative staining to PSMA while factor VIII was expressed in all cases. Seventy-five percent of the secretory-acinar epithelium of the prostatic hyperplasia specimen stained positive, confirming that the immunohistochemical technique was correctly performed. Conclusion The absence of PSMA expression in non-tumoral neovasculature supports the theory, previously suggested, that endothelial cell PSMA expression may be stimulated by one or more tumor-secreted angiogenic factors. Angiogenesis is very important in neoplasia and the endothelial expression of PSMA in tumor-associated neovasculature may represent a target for antineovasculature-based therapy. The absence of PSMA expression in CNVM suggests that PSMA may not be a potential target for antineovasculature-based therapy.Journal of Carcinogenesis. 01/2006;
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Institutions
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2008–2012
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McGill University
- Division of Ophthalmology
Montréal, Quebec, Canada
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2009
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McGill University Health Centre
Montréal, Quebec, Canada
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