Effects of glaucoma medications and preservatives on cultured human trabecular meshwork and non-pigmented ciliary epithelial cell lines

Br J Ophthalmol. 2011 Oct;95(10):1466-9. doi: 10.1136/bjophthalmol-2011-300012. Epub 2011 May 20.

Abstract

Aims: We investigated the potential cytotoxicity of various topical ophthalmic glaucoma formulations containing different preservatives in cultured human trabecular meshwork (TM) and non-pigmented ciliary epithelial (NPCE) cell lines.

Methods: We tested 0.004% travoprost preserved with either 0.015% benzalkonium chloride (BAK), sofZia or 0.001% Polyquad (PQ); and 0.005% latanoprost preserved with 0.020% BAK. We also tested a range of BAK concentrations in balanced salt solution (BSS). TM cells were treated for 10 min at 37°C with solutions diluted 1:10 to mimic the reduced penetration of topical preparations to the anterior chamber. Viability was determined by the uptake of the fluorescent vital dye calcein-AM (n = 6).

Results: BAK solutions (diluted 1:10) demonstrated a dose-dependent reduction in cell viability in both cell types (TM and NPCE). With a 1:10 dilution of 0.020% BAK, there were significantly more living NPCE cells (89 ± 6%) than TM cells (57 ± 6%; p < 0.001). In TM cells, travoprost + BAK had statistically fewer live cells (83 ± 5%) than both travoprost + sofZia (97 ± 5%) and travoprost + PQ (97 ± 6%; p < 0.05). Compared with BSS-treated NPCE cells, travoprost had statistically fewer live cells (p < 0.05) when preserved with BAK (85 ± 16%), sofZia (91 ± 6%) or PQ (94 ± 2%).

Conclusions: These results demonstrate that substitution of BAK from topical ophthalmic drugs results in greater viability of cultured TM cells, the cells involved in the conventional outflow pathway. Cultured NPCE, responsible for aqueous inflow, appear more resilient to BAK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / toxicity*
  • Benzalkonium Compounds / toxicity
  • Cell Survival
  • Cells, Cultured
  • Ciliary Body / cytology*
  • Cloprostenol / analogs & derivatives
  • Cloprostenol / toxicity
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Glaucoma / drug therapy
  • Humans
  • Latanoprost
  • Polymers / toxicity
  • Preservatives, Pharmaceutical / toxicity*
  • Prostaglandins F, Synthetic / toxicity
  • Trabecular Meshwork / drug effects*
  • Travoprost

Substances

  • Antihypertensive Agents
  • Benzalkonium Compounds
  • Polymers
  • Preservatives, Pharmaceutical
  • Prostaglandins F, Synthetic
  • Cloprostenol
  • Latanoprost
  • polyquaternium 1
  • Travoprost