| Thyroid Associated-ophthalmopathy (TAO) is a medically incurable, chronic autoimmune process that affects the retroorbital space and appears to have strong etiological links with autoimmune thyroid disease. Using sensitive diagnostic techniques, the presence of TAO can be demonstrated in the majority of patients with Graves'disease. A smaller percentage of patients with TAO and pretibial dermopathy and, even more rare, finger or toe acropachy Patients displaying one or more of these extrathyroid manifestations frequently develop severe TAO, with high concentrations of TSHR-stimulating immunoglobulins almost invariably being detectable in their sera. Clinically, although no clear correlation has been established between the presence or severity of TSHR-directed antibodies and the presence or severity of TAO, severe TAO tends to occur in the presence of high concentrations of TSHR-stimulating immunoglobulins. Thus, rather than being considered a separate disease entity, TAO may be viewed more appropriately as one manifestation within a spectrum of disease expressions that are closely associated with the autoimmune process underlying Graves' disease.and, most likely, have certain pathogenic features in common. Therefore, if an antigen shared between the affected anatomic areas in Graves' disease (thyroid gland, retroorbital space, pretibial subcutaneous connective tissue) can be envisioned, the TSHR may appear to be a logical candidate. Thus, authors are looking for more evidence that TSHR exists in tissues outside the thyroid gland, including retroorbital tissue and adipocytes by different assays and techneques, but fail to get a consistent result, and lack of systemic study on it. In our paper, we will initially detect the presence of mRNA encoding the TSHR in retroorbital tissue derived from patients with TAO and from normal individuals, further to demonstrate whether intact TSHR protein may also be expressed in these tissues. And the detection of the TSHR gene sequence is also necessary. A polymorphism in codon 52 of the TSHR gene may be present at higher frequency in female patients with severe TAO, and the resulting amino acid substitution may alter an immunologically relevant conformational epitope because it is located in a region of the TSHR that appears to be immunogenic and involved in three-dimensional folding of the TSHR. Finally, for the first time we examined histopathologic and ultrastructural changes of retroorbital fatty and connective tissue in TAO, in order to collect some evidences or provide some clew to highlight the pathogenesis.Part I Expression of thyrotropin-receptor mRNA in retroorbital tissue of healthy and thyroid associated ophthalmopathyObjective: Detect mRNA encoding TSHR in retroorbital fatty and connective tissue with TAO and healthy subjects, demonstrate that TSHR may present in retroorbital tissue and serve as common antigen in the thyroidal and extrathyroidal manifestations of TAO.Methods: Remove retroorbital fatty and connective tissues from TAO and normal controls during the operation of orbit decompression and orbital tumor resection. The total tissue RNA were isolated by single-step method of Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction and determined by reverse transcription polymerase chain reaction for TSHRmRNA.Results: 9 of 11 TAO patients and 2 of 10 normal subjects express TSHRmRNA in retroorbital tissues. 2 TAO patients and 8 controls did not find any signal of mRNA encoding TSHR. The rate of TSHRmRNA expression in TAO retroorbital tissue was 91%, in heathy subjects was 20%.Conclusion: There are mature TSHRmRNA present in TAO retroorbital tissue and highly expressed. It indicates that TSHR may be as a common antigen that responsible for thyroid gland, the retroorbital tissue and the pretibial skin.Part II Analysis of human thyrotropin receptor immunoreactivity inhuman orbital tissueObjective: We have searched for RNA encoding TSHR in TAO retroorbital fatty connective tissues on the usage of reverse transcription p... |
PDF Full Text Request