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Subspecialties Basic & Translational Research, Cornea / Ocular Surface

Chewing the Fat

Over the past few years, our eye clinic has encountered an increasing number of patients with meibomian gland dysfunction (MGD). My colleagues and I have also noticed a concurrent trend – that many of these patients also exhibit hyperlipidemia. This was interesting enough to warrant further investigation. What did we discover? That the proportion of hyperlipidemia patients with MGD was much higher than in those with normal blood lipids. This inspired us to clarify the pathological changes occurring in the meibomian gland through hyperlipidemia and to examine their mechanisms (1).

High-fat diet
 

Upon investigation, we found direct and extended evidence of high-fat diet-induced meibomian gland inflammation, largely in response to reduction of PPAR-γ signaling. Crucially, this suggests that PPAR-γ may be a potential treatment target for meibomian gland inflammation induced by a high-fat diet. We even found that rosiglitazone, a currently approved diabetes drug and stimulator of PPAR-γ signaling, suppresses this inflammation. In addition, diet control could offer another therapeutic strategy for high-fat diet-related MGD.

Along with PPAR-γ modulation, we found that activation of the MAPK and NF-κB signaling pathways are also caused by diet-induced hyperlipidemia. This dual pathway modulation promotes the infiltration of inflammatory cells and a subsequent increase in meibomian gland proinflammatory cytokine expression in mice.

Ocular surface impact
 

This follows on from our previous research, which included multiple investigations into the widespread effects of hyperlipidemia on the ocular surface. Our work ranges from studies in ApoE knockout mice – which exhibit a genetically induced form of hyperlipidemia that leads to obstructive MGD and ocular surface changes (2) – to a series of high-fat diet studies that exhibit stress and cell death on the ocular surface (3), lacrimal gland lipid accumulation and pathologic changes to the gland (4), and dysfunction of corneal endothelial cells (5).

Wider impact
 

As a highly prevalent systemic condition, hyperlipidemia can cause multiple diseases, including atherosclerosis, hypertension, coronary heart disease, diabetes, and pancreatitis. Due to the lack of corresponding research, people pay little attention to ocular diseases caused by hyperlipidemia. We hope that our research inspires not only patients with hyperlipidemia, but also clinicians – including endocrinologists and ophthalmologists – to pay more attention to the ocular complications of hyperlipidemia. We also hope our work will provide some guidance for the clinical diagnosis and treatment of hyperlipidemia-related ocular surface diseases. One challenge we face: it is still unclear whether meibomian gland inflammation is a primary or secondary response to systemic inflammation induced by hyperlipidemia. 

Our next steps are to explore the impact of hyperlipidemia on other ocular tissues. We hope to find a clear mechanism for hyperlipidemia-induced eye damage and provide guidance for the prevention of hyperlipidemia-related eye diseases in the future. We are also conducting clinical studies to investigate the effect of hyperlipidemia treatment on the condition’s ocular surface manifestations.

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  1. J Bu et al., “High-fat diet induces inflammation of Meibomian Gland,” Invest Ophthalmol Vis Sci, 62, 13 (2021). PMID: 34398199.
  2. J Bu et al., “Hyperlipidemia induces meibomian gland dysfunction,” Ocul Surf, 17, 777 (2019). PMID: 31201956.
  3. Y Wu et al., “High-fat diet induces dry eye-like ocular surface damages in murine,” Ocul Surf, 18, 267 (2020). PMID: 32120007.
  4. X He et al., “High-fat diet-induced functional and pathologic changes in lacrimal gland,” Am J Pathol, 190, 2387 (2020). PMID: 32919976.
  5. J Bu et al., “Hyperlipidemia affects tight junctions and pump function in the corneal endothelium,” Am J Pathol, 190, 563 (2020). PMID: 31945314.
About the Authors
Wei Li

Professor of Ophthalmology and Deputy Dean of the School of Medicine at Xiamen University, Director of Department Ophthalmology & Visual Science at Xiamen University, and Honorary Professor, School of Optometry & Vision Sciences, Cardiff University, UK.


Zuguo Liu

Professor of Ophthalmology and Director of Eye Institute of Xiamen University, Chairman of Ophthalmology & Visual Science Key Laboratory of Fujian Province.


Jinghua Bu

Assistant Professor of Ophthalmology and Ophthalmologist of Xiang'an Hospital of Xiamen University.


Yang Wu

Ophthalmologist of Zhongshan Hospital, Fudan University (Xiamen Branch)


Xin He

Postdoctor of Eye Institute of Xiamen University.

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