Age-related changes in the meibomian gland

Abstract

The purpose of this study was to characterize the age-related changes of the mouse meibomian gland. Eyelids from adult C57Bl/6 mice at 2, 6, 12 and 24 months of age were stained with specific antibodies against peroxisome proliferator activated receptor gamma (PPARγ) to identify differentiating meibocytes, Oil Red O(ORO) to identify lipid, Ki67 nuclear antigen to identify cycling cells, B-lymphocyte-induced maturation protein-1 (Blimp1) to identify potential stem cells and CD45 to identify immune cells. Meibomian glands from younger mice (2 and 6 months) showed cytoplasmic and perinuclear staining with anti-PPARγ antibodies with abundant ORO staining of small, intracellular lipid droplets. Meibomian glands from older mice (12 and 24 months) showed only nuclear PPARγ localization with less ORO staining and significantly reduced acinar tissue (p<0.04). Acini of older mice also showed significantly reduced (p<0.004) numbers of Ki67 stained nuclei. While Blimp1 appeared to diffusely stain the superficial ductal epithelium, isolated cells were occasionally stained within the meibomian glandduct and acini of older mice that also stained with CD45 antibodies, suggesting the presence of infiltrating plasmacytoid cells. These findings suggest that there is altered PPARγ receptor signaling in older mice that may underlie changes in cell cycle entry/proliferation, lipid synthesis and gland atrophy during aging. These results are consistent with the hypothesis that mouse meibomian glands undergo age-related changes similar to those identified in humans and may be used as a model for age-related meibomian gland dysfunction.

Volumetric Reconstruction of the Mouse Meibomian Gland Using High‐Resolution Nonlinear Optical Imaging

“…These renderings show that MG from a young mouse contains multiple, large acini with a high lipid volume, whereas MG from an old mouse have fewer acini with markedly reduced lipid volume. These findings are consistent with earlier results showing reduced gland size in older mice (Nien et al, 2009) and further indicate that aging mouse MG show acinar "dropout" similar to that detected in humans. Overall, this study demonstrates that NLO array tomography may be a useful approach to studying the 3-D structure of tissues and glands and that it provides quantitative, volumetric measurements with femtolitre resolution.…”

“…Recently, we have shown that the MG of mice develop age-related changes similar to those observed in humans, including reduced gland size and decreased proliferative potential (Nien et al, 2009). Since previous studies of human MGD using transillumination biomicroscopy (meibography) have identified "gland dropout" as a pathognomonic feature, (Jester et al, 1982) the purpose of this study was to develop an imaging approach to generate quantifiable volumetric reconstructions of the mouse MG that could assess gland "dropout" and measure the total, cellular, and lipid volume.…”

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

“…Modifications on MG structure have been identified with age as, an altered localization of the peroxisome proliferator-activated receptor-ɣ (PPAR-ɣ), a lipid-activated hormone receptor that regulates lipid synthesis and cell differentiation [16,17] or MG atrophy [18]. In research on mouse model, some authors have found changes in the mucocutaneous junction and glandular atrophy through a loss of meibocyte progenitors [18].…”

Associations with Meibomian Gland Atrophy in Daily Contact Lens Wearers

“…1,2 This altered lipid production could subsequently result in increased tear evaporation, increased tear osmolality, and dryness symptoms. 3,4 There is currently little information available to prove a direct link between meibomian gland atrophy and CL discomfort.…”