Archives of Ophthalmology · 2011 · 166 citations · 42 references
MedicineDermatologyPathologyAgingDermatopathologyImmunopathologyAge-related ChangesCellular AgingEyelid Gland DisordersImmunohistochemistryAcinar Cell DysfunctionBasal Epithelial CellsDermatologic DisordersDermatologic HistopathologyMeibomian GlandsPeroxisome Proliferator Receptor SignalingPeroxisome Proliferator-activated Receptor SignalingPeroxisome Proliferator-activated Receptors
OBJECTIVE: To identify age-related changes in human meibomian glands that may be associated with meibomian gland dysfunction (MGD). METHODS: Excess eyelid tissue from 36 patients (age range, 18-95 years, 19 female, 17 male) who underwent canthoplasty procedures were used. Dermatologic history, age, and presence of MGD were recorded. Samples were frozen, sectioned, and stained with specific antibodies against peroxisome proliferator-activated receptor γ (PPARγ) to identify meibocyte differentiation, Ki67 nuclear antigen to identify cycling cells, and CD45 to identify inflammatory cell infiltration. RESULTS: Staining for PPARγ showed cytoplasmic and nuclear localization in the 2 youngest subjects (ages, 18 and 44 years). Older individuals (>60 years) showed predominantly nuclear staining, with cytoplasmic staining limited to the basal acinar cells in 17 of 31 subjects. The number of Ki67 positively stained basal cells were significantly elevated in the younger compared with older subjects based on linear regression analysis (r(2) = 0.35; P < .001). There was also a significant correlation between MG expression grade and CD45 cell infiltration (r = 0.414; P = .05). CONCLUSIONS: These results indicate that aging human meibomian glands show decreased meibocyte differentiation and cell cycling that is associated with the development of MGD. Findings also suggest that altered PPARγ signaling may lead to acinar atrophy and development of an age-related hyposecretory MGD. CLINICAL RELEVANCE: Meibomian gland dysfunction and evaporative dry eye are common age-related eyelid disorders. Understanding the underlying mechanism of MGD may lead to the development of novel therapeutic strategies to treat this disease.
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PPARγ Is Required for the Differentiation of Adipose Tissue In Vivo and In Vitro
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Transcriptional regulation of adipogenesis
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