In our previous blog about cell cultures and preservatives, we discussed the importance of using the correct study design to derive valid scientific conclusions. The meibomian gland (MG) cell culture studies contained tantalizing and useful scientific information, but this has been drowned out by fearmongering about an interpretation that cannot be extrapolated from the MG cell culture studies.

Many of us have heard that preservatives like paraben, phenoxyethanol, tea tree oil, or chlorphenesin can “kill” meibomian gland cells. The MG studies1,2 did indeed “show” this, but it’s also true that mammalian cell cultures like the MG cell cultures require stringent growing conditions, and any change to the growth medium, pH, or environmental factors can be fatal to these cells. We can splash water into our eyes without morbid injury to our meibomian glands, but doing the same to MG cell cultures would be deadly. The MG cell cultures were also used to demonstrate the toxicity of glaucoma preservatives3,4 like benzalkonium chloride (BAK), which is indeed toxic to the ocular surface. But using the wrong study design to “prove” this is like using a broken clock to tell time – it’ll be occasionally right.

The MG cell culture studies were excellent and well-designed, but what did they really show? Scientists know that in-vitro cell cultures are excellent models for studying biochemical cascades. In the case of the MG cell cultures, the studies demonstrated changes in certain enzymatic activities associated with cellular proliferation and metabolism (Akt pathway) that occur with cellular death or apoptosis. These biochemical changes occur regardless of what triggered the cellular injury, whether from tea tree oil, preservatives, or even water. The biochemical results provide scientists with insights into the cascades and proteins involved in cellular death. This information provides a guide to which proteins or pathways should be targeted to prevent or retard cellular death and, hopefully, increase the longevity of cells. 

Science is about hope, not fear. We fear what we do not know. Now that we understand the true meaning of the MG cell culture studies, we can relinquish our fear and celebrate the possibility that these studies may enable scientists to design drugs to help us live longer, better lives.

1. Chen D, Wang J, Sullivan DA, Kam WR, Liu Y. Effects of Terpinen-4-ol on Meibomian Gland Epithelial Cells In Vitro. Cornea. 2020 Dec;39(12):1541-1546.
2. Wang J, Liu Y, Kam WR, Li Y, Sullivan DA. Toxicity of the cosmetic preservatives parabens, phenoxyethanol and chlorphenesin on human meibomian gland epithelial cells. Exp Eye Res. 2020 Jul;196:108057.
3. Chen X, Sullivan DA, Sullivan AG, Kam WR, Liu Y. Toxicity of cosmetic preservatives on human ocular surface and adnexal cells. Exp Eye Res. 2018 May;170:188-197.
4. Rath A, Eichhorn M, Träger K, Paulsen F, Hampel U. In vitro effects of benzalkonium chloride and prostaglandins on human meibomian gland epithelial cells. Ann Anat. 2019 Mar;222:129-138.