Histopathology and selective biomarker expression in human meibomian glands

Abstract

Background/aimsMeibomian gland dysfunction (MGD) is the most common form of evaporative dry eye disease, but its pathogenesis is poorly understood. This study examined the histopathological features of meibomian gland (MG) tissue from cadaver donors to identify potential pathogenic processes that underlie MGD in humans.MethodsHistological analyses was performed on the MGs in the tarsal plates dissected from four cadaver donors, two young and two old adults, including a 36-year-old female (36F) and three males aged 30, 63 and 64 years (30M, 63M and 64M).ResultsThe MGs of 36F displayed normal anatomy and structure, whereas the MGs of 30M showed severe ductal obstruction with mild distortion. The obstruction was caused by increased cytokeratin levels in association with hyperproliferation, but not hyperkeratinisation. In two older males, moderate to severe MG atrophy was noted. Cell proliferation was significantly reduced in the MG acini of the two older donors as measured by Ki67 labelling index (6.0%±3.4% and 7.9%±2.8% in 63M and 64M, respectively) when compared with that of the two younger donors (23.2%±5.5% and 16.9%±4.8% in 30M and 36F, respectively) (p<0.001). The expression patterns of meibocyte differentiation biomarkers were similar in the older and younger donors.ConclusionOur histopathological study, based on a small sample size, suggests potentially distinct pathogenic mechanisms in MGD. In the young male adult, hyperproliferation and aberrant differentiation of the central ductal epithelia may lead to the obstruction by overproduced cytokeratins. In contrast, in older adults, decreased cell proliferation in acinar basal epithelia could be a contributing factor leading to MG glandular atrophy.

Candidate Molecular Compounds as Potential Indicators for Meibomian Gland Dysfunction

“…The study finding suggested that the central ductal epithelia’s abnormal differentiation and proliferation may be responsible for the ductal obstruction. This study also showed that ductal epithelial abnormal differentiation and proliferation alone, barring any conspicuous hyperkeratinization, can obstruct the meibomian glands ( 93 ). The decline in acinar cell proliferation and renewal was purported to be the underpinning instigator of meibomian gland atrophy with aging ( 93 ).…”

“…This study also showed that ductal epithelial abnormal differentiation and proliferation alone, barring any conspicuous hyperkeratinization, can obstruct the meibomian glands ( 93 ). The decline in acinar cell proliferation and renewal was purported to be the underpinning instigator of meibomian gland atrophy with aging ( 93 ). This evidence shows that overexpression of hyperproliferative keratins in meibum may be potential biomarkers to detect obstructive MGD accurately ( 93 ).…”

“…It has been noted that keratin mixes into the tear film’s lipid layer and can destabilize the lipid layer in vitro ( 25 , 92 ). Keratin 10 and keratin 1 are considered to be essential keratinization markers because they are present in terminally differentiated keratinocytes ( 93 ). To confirm whether the ductal epithelia’s hyperkeratinization is responsible for the meibomian glands’ ductal obstruction, some researchers studied the expression patterns of Keratin 10 and keratin 1 in the four donors’ meibomian glands ( 93 ).…”

“…Keratin 10 and keratin 1 are considered to be essential keratinization markers because they are present in terminally differentiated keratinocytes ( 93 ). To confirm whether the ductal epithelia’s hyperkeratinization is responsible for the meibomian glands’ ductal obstruction, some researchers studied the expression patterns of Keratin 10 and keratin 1 in the four donors’ meibomian glands ( 93 ). The study finding suggested that the central ductal epithelia’s abnormal differentiation and proliferation may be responsible for the ductal obstruction.…”

“…The decline in acinar cell proliferation and renewal was purported to be the underpinning instigator of meibomian gland atrophy with aging ( 93 ). This evidence shows that overexpression of hyperproliferative keratins in meibum may be potential biomarkers to detect obstructive MGD accurately ( 93 ). Again, other researchers have demonstrated that cytokeratins CK1, CK10, CK13, CK14, and CK19 may be candidate biomarkers within human eyelid tissue to uncover the meibomian gland ducts’ keratinization around the mucocutaneous junction ( 54 , 94 ).…”