Molecular pathology of Müller's muscle in Graves' ophthalmopathy

Context: Upper lid retraction is a common sign in Graves' ophthalmopathy (GO). Whether M?ller's muscle is involved in upper lid retraction has not been fully elucidated. Objective: The objective of the study was to understand the molecular pathology of M?ller's muscle in GO. Design/Setting/ Participants: A method for measurement of histological changes was developed and used to correlate severity and expression of cell-specific genes in GO. Main Outcome Measures: Histological changes, clinical severity of upper lid retraction, and mRNA expression in M?ller's muscle in GO were measured. Results: The degree of fibrosis correlates with severity of upper lid retraction. Macrophage infiltration was increased in fibrotic areas, consistent with higher levels of macrophage-colony stimulating factor mRNA. Levels of peroxisome proliferator-activated receptor-γ mRNA were up-regulated and correlated with fat infiltration. Decreased muscle mass correlated with lower myocardin mRNA expression. The expression of c-kit levels was decreased in diseased muscles, consistent with diminished mast cell numbers. Conclusion: The pathological changes of M?ller's muscle correlate with clinical severity of upper lid retraction in GO. Patterns of gene expression appear to correlate with the histopathological changes in this disease process. Copyright ? 2006 by The Endocrine Society.