Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00174057
Status:
UNKNOWN
Last Update Posted:
2005-09-15
First Post:
2005-09-13
Brief Title:
The Role of TSH Receptor PPAR-r IGF-1R IGF and Cytokines in Different Stages of GravesOphthalmopathy
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
None
Status:
UNKNOWN
Status Verified Date:
2005-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The exact mechanism of the pathogenesis of Graves ophthalmopathy is still unknown Histopathologically extraocular muscle inflammation and orbital fat inflammation are two prominent changes In the past year we had investigated the morphological features of the Müller muscle in patients with thyroid lid retraction using the special stain and immunohistochemistry In our findings the smooth muscle cells in the diseased group were replaced by variable adipose and fibrosis tissues
In recent years TSHR has been verified to express in orbital connective tissue and extra-ocular muscle From functional studies and an increase in adipogenesis in cultured fibroblasts with expression of TSHR protein the role not only the target but effector cells in orbital fibroblasts were validated Quantitative RT-PCR may help to differentiate whether a less extent of expression at the end stage or low protein amount to be detected
In recent years the diverse phenotypes of orbital fibroblasts with regard to expression of Thy-1 protein or not had been reported from several studies the investigators believed heterogeneity in orbital fibroblast may determine the clinical presentation of Gravesophthalmopathy We also are curious to know if the phenotypic heterogeneity of the fibroblasts in the ocular adnexal and orbital tissues correlates to distinct morphological features of adipogenesis and fibrosis
Moreover increased CD40 expression in skin fibroblasts were noted from patients with systemic sclerosis Expression of IGF-I and IGF-IR seemed to be up-regulated in processes of several fibrotic diseases A nuclear transcription factor PPAR-γ has been verified to have a close relationship with adipogenesis We hypothesize that some immunological processes involve the ocular adnexal and orbital tissues which result in various ophthalmological manifestations
The purpose of this study is to investigate the different stage of the ocular adnexal and orbital tissues to identify the pathogenesis of Graves ophthalmopathy by frozen sections with Immunohistochemistry mRNA expression of TSH receptor PPAR-γ IGF-1R and IGF-1 and different cytokines using quantitative RT-PCR and flow cytometry at the acute and stable stage in GO
In recent years TSHR has been verified to express in orbital connective tissue and extra-ocular muscle From functional studies and an increase in adipogenesis in cultured fibroblasts with expression of TSHR protein the role not only the target but effector cells in orbital fibroblasts were validated Quantitative RT-PCR may help to differentiate whether a less extent of expression at the end stage or low protein amount to be detected
In recent years the diverse phenotypes of orbital fibroblasts with regard to expression of Thy-1 protein or not had been reported from several studies the investigators believed heterogeneity in orbital fibroblast may determine the clinical presentation of Gravesophthalmopathy We also are curious to know if the phenotypic heterogeneity of the fibroblasts in the ocular adnexal and orbital tissues correlates to distinct morphological features of adipogenesis and fibrosis
Moreover increased CD40 expression in skin fibroblasts were noted from patients with systemic sclerosis Expression of IGF-I and IGF-IR seemed to be up-regulated in processes of several fibrotic diseases A nuclear transcription factor PPAR-γ has been verified to have a close relationship with adipogenesis We hypothesize that some immunological processes involve the ocular adnexal and orbital tissues which result in various ophthalmological manifestations
The purpose of this study is to investigate the different stage of the ocular adnexal and orbital tissues to identify the pathogenesis of Graves ophthalmopathy by frozen sections with Immunohistochemistry mRNA expression of TSH receptor PPAR-γ IGF-1R and IGF-1 and different cytokines using quantitative RT-PCR and flow cytometry at the acute and stable stage in GO
Detailed Description:
The exact mechanism of the pathogenesis of Graves ophthalmopathy GO is still unknown Histopathologically extraocular muscle inflammation due to lymphoid infiltration edema and interstitial fibrosis and increased glycosaminoglycan deposition and orbital fat inflammation are two prominent changes There are various manifestations including ocular adnexal tissues inflammation proptosis lid retraction extraocular movement limitation and compressive optic neuropathy In the past year we had investigated the morphological features of the Müller muscle in patients with thyroid lid retraction using the special stain and immunohistochemistry in formalin-fixed paraffin-embbeded FFPE sections In our findings the smooth muscle cells in the diseased group were replaced by variable adipose and fibrosis tissues Two distinct features in the disease group seem to be notable for further investigation
In recent years TSHR a putative autoantigen has been verified to express in orbital connective tissue and extra-ocular muscle In addition they were further demonstrated to express on the surface of cultured orbital fibroblasts and orbital adipose tissue in patients with GO in several laboratories From functional studies and an increase in adipogenesis in cultured fibroblasts with expression of TSHR protein the role not only the target but effector cells in orbital fibroblasts were validated7 We used immunohistochemistry to verify the existence of TSHR on the fibroblasts within the Müller muscle and the positive staining is manifested in only18 of patients It may due to a less extent of expression at the end stage We are very curious to know if there any difference on the expression of TSHR between orbital specimens from patients with acute and those with stable stage Quantitative RT-PCR may help to differentiate whether a less extent of expression at the end stage or low protein amount to be detected
In recent years the diverse phenotypes of orbital fibroblasts with regard to expression of Thy-1 protein or not had been reported from several studies the investigators believed heterogeneity in orbital fibroblast may determine the clinical presentation of Graves ophthalmopathy We also are curious to know if the phenotypic heterogeneity of the fibroblasts in the ocular adnexal and orbital tissues correlates to distinct morphological features of adipogenesis and fibrosis In addition systemic or local pro-inflammatory cytokines may contribute to turn on and turn off the expression of different roles of the fibroblasts
Moreover increased CD40 expression in skin fibroblasts were noted from patients with systemic sclerosis Expression of IGF-I and IGF-IR seemed to be up-regulated in processes of several fibrotic diseases A nuclear transcription factor PPAR-γ has been verified to have a close relationship with adipogenesis In our previous study the smooth muscle cells in the diseased Mullers muscle were replaced by variable adipose and fibrosis tissues The increased adipose and fibrosis tissue ex vivo of the Müller muscle may result from over-action of some biochemical markers in the fibroblasts infiltrating around muscle cells We hypothesize that some immunological processes involve the ocular adnexal and orbital tissues which result in various ophthalmological manifestations
The purpose of this study is to investigate the different stage acute or stable stage of the ocular adnexal and orbital tissues including orbital fat extraocular muscles orbicularis muscles and eyelid fat to identify and validate the pathogenesis of Graves ophthalmopathy by frozen sections of the ocular adnexal and orbital tissues with Immunohistochemistry IHA Thy-1 and PPARγ mRNA expression of TSH receptor PPAR-γ IGF-1R and IGF-1 and different cytokines IL-1β IL-4 IL-6 IL-8 using quantitative RT-PCR and flow cytometry at the acute and stable stage in GO
In recent years TSHR a putative autoantigen has been verified to express in orbital connective tissue and extra-ocular muscle In addition they were further demonstrated to express on the surface of cultured orbital fibroblasts and orbital adipose tissue in patients with GO in several laboratories From functional studies and an increase in adipogenesis in cultured fibroblasts with expression of TSHR protein the role not only the target but effector cells in orbital fibroblasts were validated7 We used immunohistochemistry to verify the existence of TSHR on the fibroblasts within the Müller muscle and the positive staining is manifested in only18 of patients It may due to a less extent of expression at the end stage We are very curious to know if there any difference on the expression of TSHR between orbital specimens from patients with acute and those with stable stage Quantitative RT-PCR may help to differentiate whether a less extent of expression at the end stage or low protein amount to be detected
In recent years the diverse phenotypes of orbital fibroblasts with regard to expression of Thy-1 protein or not had been reported from several studies the investigators believed heterogeneity in orbital fibroblast may determine the clinical presentation of Graves ophthalmopathy We also are curious to know if the phenotypic heterogeneity of the fibroblasts in the ocular adnexal and orbital tissues correlates to distinct morphological features of adipogenesis and fibrosis In addition systemic or local pro-inflammatory cytokines may contribute to turn on and turn off the expression of different roles of the fibroblasts
Moreover increased CD40 expression in skin fibroblasts were noted from patients with systemic sclerosis Expression of IGF-I and IGF-IR seemed to be up-regulated in processes of several fibrotic diseases A nuclear transcription factor PPAR-γ has been verified to have a close relationship with adipogenesis In our previous study the smooth muscle cells in the diseased Mullers muscle were replaced by variable adipose and fibrosis tissues The increased adipose and fibrosis tissue ex vivo of the Müller muscle may result from over-action of some biochemical markers in the fibroblasts infiltrating around muscle cells We hypothesize that some immunological processes involve the ocular adnexal and orbital tissues which result in various ophthalmological manifestations
The purpose of this study is to investigate the different stage acute or stable stage of the ocular adnexal and orbital tissues including orbital fat extraocular muscles orbicularis muscles and eyelid fat to identify and validate the pathogenesis of Graves ophthalmopathy by frozen sections of the ocular adnexal and orbital tissues with Immunohistochemistry IHA Thy-1 and PPARγ mRNA expression of TSH receptor PPAR-γ IGF-1R and IGF-1 and different cytokines IL-1β IL-4 IL-6 IL-8 using quantitative RT-PCR and flow cytometry at the acute and stable stage in GO
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None