Hyperglycemia Induces Meibomian Gland Dysfunction

Guo, Yanjie; Zhang, Houjian; Zhao, Zhongyang; Luo, Xin; Zhang, Minjie; Bu, Jinghua; Liang, Mengya; Wu, Han; Yu, Jingwen; He, Hui; Zong, Rongrong; Chen, Yongxiong; Liu, Zuguo; Li, Wei

doi:10.1167/iovs.63.1.30

Cited by 28 publications

(12 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 1 , 35 We found that proinflammatory stress could facilitate lipogenesis and accelerate the terminal fate of HMGECs related to the overactivation of apoptosis and autophagy, which may play a pathologic role in lipid abnormalities and acini dropout in MGD. Consistent with our findings, Guo et al 10 recently reported that there was a prominent proinflammatory cytokine response, lipid accumulation, glandular dropout, and cell death in rats with MGD induced by hyperglycemia. Kim et al 54 also suggested that autophagy was initiated and mediated for cellular disintegration during the late differentiation of HMGECs.…”

Section: Discussionsupporting

confidence: 93%

“… 9 In addition, prominent inflammatory cell infiltration and proinflammatory cytokine responses were detected in the MG microenvironment in a rodent MGD model induced by hyperlipidemia and hyperglycemia. 10 , 11 Abnormal accumulation of intraductal lipids from meibocytes and hyperkeratinization of MG ductal cells are important features of MGD. 8 , 12 Studies have reported that the pathology of ductal hyperkeratinization involves the overexpression of keratin 1 in MG ductal cells induced by proinflammatory stimulation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Melatonin Attenuates LPS-Induced Proinflammatory Cytokine Response and Lipogenesis in Human Meibomian Gland Epithelial Cells via MAPK/NF-κB Pathway

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose Inflammation contributes to the development of meibomian gland dysfunction (MGD) under specific disease conditions, but the underlying mechanisms remain elusive. We examined whether lipopolysaccharide (LPS) induced a proinflammatory cytokine response and lipogenesis in human meibomian gland epithelial cells (HMGECs) and whether melatonin (MLT), a powerful anti-inflammatory regent in the eyes, could protect against LPS-induced disorders. Methods Human meibomian gland (MG) tissues and immortalized HMGECs were stained to identify Toll-like receptor (TLR) 4 and MLT receptors (MT 1 and MT 2 ). HMGECs were pretreated with or without MLT and then stimulated with LPS. Then, TLR4 activation, cytokine levels, lipid synthesis, apoptosis, autophagy, and MAPK/NF-κB factor phosphorylation in HMGECs were analyzed. Results TLR4, MT 1 , and MT 2 were expressed in human MG acini and HMGECs. Pretreatment with MLT inhibited the TLR4/MyD88 signaling and attenuated proinflammatory cytokine response and lipogenesis in LPS-stimulated HMGECs, which manifested as decreased production of cytokines (IL-1β, IL-6, IL-8, and TNF-α), reduced lipid droplet formation, and downregulated expression of meibum lipogenic proteins (ADFP, ELOVL4, and SREBP-1). Phospho-histone H2A.X foci, lysosome accumulation, and cytoplasmic cleaved caspase 3/LC3B-II staining were increased in LPS-stimulated HMGECs, indicating enhanced cell death mediated by apoptosis and autophagy during LPS-induced lipogenesis. MLT downregulated cleaved caspase 3 levels and the Bax/Bcl-2 ratio to alleviate apoptosis and ameliorated the expression of Beclin 1 and LC3B-II to inhibit autophagy. The protective mechanisms of MLT include the inhibition of MAPK and NF-κB phosphorylation. Conclusions MLT attenuated lipogenesis, apoptosis, and autophagy in HMGECs induced by proinflammatory stimuli, indicating the protective potential of MLT in MGD.

show abstract

Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Melatonin Attenuates LPS-Induced Proinflammatory Cytokine Response and Lipogenesis in Human Meibomian Gland Epithelial Cells via MAPK/NF-κB Pathway

Liu

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…The LFU is essential in producing and maintaining a healthy tear film to help preserve ocular surface homeostasis. Previous studies have shown that diabetes produced altered morphology in the LFU structures, with decreased secretory granules in the lacrimal gland, decreased conjunctival goblet cell density, and decreased acinar size in Meibomian glands [ 25 – 27 ]. We found morphological alterations in the diabetic LFU after 6–7 weeks of hyperglycemia, with topical NTX altering only goblet cell deficits after 10 days of treatment.…”

Section: Discussionmentioning

confidence: 99%

Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats

Diaz,

Sassani,

Zagon

et al. 2024

Exp. Biol. Med.

View full text Add to dashboard Cite

Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.

show abstract

“…Recently, the inflammatory microenvironment of the MG under diabetic conditions was indicated. It was also found that inflammatory cell infiltration apparently increases and inflammatory cytokine expression was significantly elevated in the MG of DM rats [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of meibomian gland dysfunction in type 2 diabetes with dry eye disease: a non-randomized controlled trial

Yang

Liu

et al. 2023

BMC Ophthalmol

View full text Add to dashboard Cite

Background The purpose of this investigation was to evaluate the morphology and physiological function of the meibomian glands between type 2 diabetics with dry eye disease (DED) and control subjects. Doing so will help to better reveal the pathologic mechanisms of meibomian gland dysfunction (MGD) and DED in type 2 diabetes mellitus (T2DM). Methods Ninety subjects were divided into the following four groups: DM-DED group: T2DM patients with DED (n = 30); DM control group: DM patients without DED (n = 18); DED group: DED patients without DM (n = 26); and normal control group: normal subjects (n = 16). All participants administered the ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), noninvasive Keratograph tear film break-up time (NIKBUT), Schirmer I test (SIT), corneal fluorescein staining (CFS), eyelid margin abnormality examinations, meibum quality and meibomian gland (MG) dropout evaluations. Results The percentage of MG dropout in the upper and lower lids was significantly higher in the DM-DED group than the DED group (P < 0.05 or P < 0.01). However, there was no significant difference in other MG parameters between these two groups. Oppositely, Significant difference was observed in all of MG parameters except MG dropout in the lower lids comparing DM group with normal controls (P < 0.05 or P < 0.01). While the SIT values decreased in the DM-DED group compared to the DED group (P < 0.05), no significant differences were found in the values of other tear parameters. Conclusions The higher prevalence and increased severity of MGD was found in patients with both T2DM and DED compared to those only with DED. Trial registration Chinese Clinical Trial Registry ChiCTR1800019939, date of registration December 9, 2018, prospectively registered.

show abstract

Hyperglycemia Induces Meibomian Gland Dysfunction

Cited by 28 publications

References 56 publications

Melatonin Attenuates LPS-Induced Proinflammatory Cytokine Response and Lipogenesis in Human Meibomian Gland Epithelial Cells via MAPK/NF-κB Pathway

Melatonin Attenuates LPS-Induced Proinflammatory Cytokine Response and Lipogenesis in Human Meibomian Gland Epithelial Cells via MAPK/NF-κB Pathway

Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats

Evaluation of meibomian gland dysfunction in type 2 diabetes with dry eye disease: a non-randomized controlled trial

Contact Info

Product

Resources

About