Pathogenei of Grave Ophthalmopathy: Implication for Prediction, Prevention, and Treatment Original Reearch Article

Purpoe To review current concept regarding the pathogenei of Grave ophthalmopathy (GO). We have preented thi information in the context of potential target ite for novel dieae therapie. Deign Review of recent literature. Method ynthei of recent literature. Reult Enlargement of the extraocular mucle bodie and expanion of the orbital fatty connective tiue i apparent in patient with GO. Thee change reult from abnormal hyaluronic acid accumulation and edema within thee tiue and expanded volume of the orbital adipoe tiue. Recent tudie have uggeted that the increae in orbital fat volume i caued by timulation of adipogenei within thee tiue. The orbital fibroblat appear to be the major target cell of the autoimmune proce in GO. A ubet of thee cell i capable of producing hyaluronic acid and differentiating into mature adipocyte, given appropriate timulation. In addition, orbital fibroblat from patient with GO have been hown to diplay immunoregulatory molecule and to expre both thyrotropin receptor (THR) and inulin-like growth factor 1 receptor (IGF-1R). Increaed THR expreion in the GO orbit appear to be the reult of timulated adipocyte differentiation. The activation of IGF-1R on orbital fibroblat by immunoglobulin from GO patient reult in increaed production of both hyaluronic acid and molecule that timulate the infiltration of activated T cell into area of inflammation. Concluion Potential target for novel therapeutic agent to be ued in GO include blocking T-cell cotimulation, depleting B cell, inhibiting cytokine action, targeting the IGF-1R or the THR, and preventing connective tiue remodeling.