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Molecular Pathology of Müller’s Muscle in Graves’ Ophthalmopathy

Graduate Institute of Clinical Medicine (M.-J.S., L.-M.C.), National Taiwan University School of Medicine, Taipei 10494, Taiwan; Departments of Ophthalmology (S.-L.L.), Pathology (K.-T.K.), and Internal Medicine (L.-M.C.), National Taiwan University Hospital, Taipei 10494, Taiwan; Department of Ophthalmology (M.-J.S.), Shin Kong Memorial Hospital, Taipei 111, Taiwan; Department of Medicine (M.-J.S.), College of Medicine, Hsinchuang, Fu-Jen Catholic University, Taipei Hsien 24205, Taiwan; Division of Molecular Medicine (T.J.S.), Harbor-University of California, Los Angeles Medical Center, Torrance, California 90502; and David Geffen School of Medicine (T.J.S.), University of California, Los Angeles, California 90095

Address all correspondence and requests for reprints to: Dr. Lee-Ming Chuang, Department of Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan. E-mail: leeming{at}ha.mc.ntu.edu.tw.

Context: Upper lid retraction is a common sign in Graves’ ophthalmopathy (GO). Whether Müller’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 Müller’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 Müller’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- 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 Müller’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.