Yang Liu, M.D.

What is Meibomian Gland Dysfunction?

Dr. Liu’s principle research projects have focused on developing a potential therapy for meibomian gland dysfunction (MGD), which is the leading cause of dry eye disease (DED) in the world. DED affects hundreds of millions of people, predominantly women, and is one of the most frequent reasons patients visit their eye-care practitioners. The impact of moderate-to-severe DED is comparable to conditions such as severe angina, and is associated with significant pain, role limitations, low vitality, and poor general health. There is no cure for MGD.

Research Discoveries

Dr. Liu has discovered that azithromycin (AZM), a macrolide antibiotic, can directly stimulate the function of human meibomian gland epithelial cells (HMGECs). More specifically, she has found that AZM stimulates their differentiation, enhances the quality and quantity of their lipid production, and promotes their holocrine secretion. These findings are clinically significant because topical AZM is the most commonly prescribed MGD treatment in the United States, but its use is "off-label." This antibiotic had been presumed to be effective because of its anti-inflammatory and antibacterial actions, which may suppress the MGD-associated conjunctival inflammation (i.e., posterior blepharitis) and growth of lid bacteria. To explain her results, Dr. Liu hypothesized that AZM’s phospholipidosis-like action is due to its cationic amphiphilic drug (CAD) nature. Dr. Liu has shown this hypothesis to be correct, which may soon lead to another CAD antibiotic, solithromycin, being tested in a clinical trial for the treatment of MGD.

Since those initial studies, Dr. Liu discovered that: 1) insulin-like growth factor-1 can enhance the differentiative effects of AZM on HMGECs, 2) omega-3 and omega-6 fatty acids can act directly on these cells to influence the quality and quantity of intracellular lipids, and 3) growth hormone can significantly influence the size and morphology of the meibomian gland. Dr. Liu also learned that internationally proposed treatments for DED, including cyclosporine A (an interleukin-1 receptor antagonist), a P2Y2 receptor agonist, and rebamipide, do not influence the proliferation or differentiation of IHMGECs. More recently, Dr. Liu has discovered that insulin stimulates IHMGECs and that high glucose is toxic for IHMGECs. These results indicate that insulin resistance/deficiency and hyperglycemia are deleterious for HMGECs and may help explain why type II diabetes is a risk factor for MGD. Overall, Dr. Liu’s findings are novel, unique, and compelling, and have led to her development of possible innovative strategies to treat MGD and the associated DED.

H-index

8 (Google Scholar, as of August 2017)

Selected Publications

Dr. Liu has published more than 10 peer-reviewed articles. Below is a list of selected publications. View her publications on PubMed.

1. Jones L, Downie LE, Korb D, Benitez-del-Castillo JM, Dana R., Deng SX, Dong PN, Geerling G., Hida RY, Liu Y, Seo, KY. TFOS DEWS II management and therapy report. The Ocular Surface. 2017;15(3), pp.575-628.
2. Liu Y, Kam WR, Ding J, Sullivan DA. Can tetracycline antibiotics duplicate the ability of azithromycin to stimulate meibomian gland epithelial cell differentiation? Cornea. 2015;34:342-346.
3. Liu Y, Ding J. The Combined Effect of Azithromycin and Insulin-Like Growth Factor-1 on Cultured Human Meibomian Gland Epithelial Cells. Invest Ophthalmol Vis Sci. 2014;Mar;55(9):5596.
4. Liu Y, Kam WR, Ding J, Sullivan DA. One man's poison is another man's meat: Using azithromycin-induced phospholipidosis to promote ocular surface health. Toxicology. 2014;320:1–5.
5. Liu Y, Kam WR, Ding J, Sullivan DA. Effect of azithromycin on lipid accumulation in immortalized human meibomian gland epithelial cells. JAMA Ophthalmology. 2014;132:226-228.

Patents

For a complete list of Dr. Liu’s patents, download her CV [PDF].

Stimulation of Human Meibomian Gland Function
US 20150141328 A1