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Lixing W Reneker, Rebecca T Irlmeier, Ying-Bo Shui, Ying Liu, Andrew J W Huang; Protein Markers in Human Meibomian Glands: Implications on Pathogenic Mechanisms of Meibomian Gland Dysfunction (MGD). Invest. Ophthalmol. Vis. Sci. 2018;59(9):3806.
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© ARVO (1962-2015); The Authors (2016-present)
Ductal obstruction and acinar atrophy of Meibomian glands (MGs) are the common pathologies of MGD in humans. To investigate the pathogenic mechanisms of MGD, we investigated the expression of various protein markers in MGs of human cadaver donors.
Tarsal plates were removed from eyelids of four adult donors, including one 36 year-old female (referred as 36F), and three males at age of 30, 63 and 64 (referred as 30M, 63M and 64M, respectively). Tissues were processed for histology and paraffin sections were stained with hematoxylin and eosin. Immunohistochemistry was performed to examine the expression of cell proliferation and differentiation markers in MG acinar and ductal epithelial cells.
Histological examination revealed normal anatomy of MGs in the 36F whereas mild ductal distortion with ductal obstruction in the MGs of 30M. Moderate to severe MG atrophy characterized by gland shortening and dropout was noted in the two older donors (63M and 64M). Cell proliferation marker, Ki67, was notably reduced in the acinar basal cells of MGs of 63M, when compared to those of 36F’s MGs. Expression patterns for meibocytes differentiation markers, including peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN) and elongation of very long chain fatty acids protein 4 (ELOVL4), were similar between the young (36F) and the older (64M) MGs. Using various keratin-specific antibodies, including those against keratin 10 (K10), K14, K16 and its pairing keratin K6a, we found that hyperproliferation of ductal epithelial cells along with substantial accumulation of K16 and K6a in the main MG duct of MGs of the 30M.
Evaluation of protein markers in MG has revealed two distinct pathogenic mechanisms of MGD. In aged MGs, decrease of cell proliferation in acinar basal cells likely attenuates MG holocrine secretion, thus lead to glandular atrophy and dropouts. In contrast, hyper-proliferation of ductal epithelial cells associated with over-production of K16/K6a leads to ductal obstruction in patients with MGD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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