Mechanisms of BAK toxicity in a human trabecular meshwork cell line (Drs Cindy Hutnik, Angela Q. Zhang, Christopher Byrne, Grayson A. Roumeliotis, Cindy Shao, Hong Liu)
/In the previous paper that I summarized on this blog, the authors looked at whether Benzalkonium Chloride (BAK) exposure was correlated with worsening prognosis for glaucoma surgery. This paper looks at the mechanism of toxicity of BAK on a trabecular meshwork cell line and its possible effect on gap junctions. It was presented at 1055hrs on 10Jun2011 during the Canadian Glaucoma Society portion of the 74th annual meeting of the Canadian Ophthalmological Society in Vancouver, BC. Although it has been some months now since the meeting, I have been working on editing my notes from the conference to add to this blog to allow for further discusssion amongst my readers.
BAK still a detective story in glaucoma and this is one of those controversies. This follows well with the last talk, which was the surgical outcomes after patients were exposed to BAK in glaucoma drops, with a bench study. With no new classes of glaucoma medications since 1996, there is increased focus on preservatives and whether they are toxic. Is this as bad as the buzz on the street?
There is still a traditional paradigm of adding medications on top of each other which can further pile up potential toxicity. Note concentrations range from 0.004 to 0.02% between different glaucoma medications. Most concentrations tried in the lab were able to kill all culture epithelial cells easily. Is it possible in vivo that the concentrations reach adequate dose to damage TM? They looked at structural damage and it did not seem to effect structure so next was to check for function of these HTM cells. HTM cells showed time and dose dependent decrease in cell viability when treated with different dosages for 1 to 30 minutes. Connexin-43 up‐regulation enhanced cell viability and down‐regulation contributed to further cellular death.
A couple of questions to think about…does HTM cell damage raise the IOP and give us more longterm problems by raising IOP. Next steps therefore include looking more at these function studies.