Implant levels of bimatoprost yield significant upregulation in MMP1 in TM cells

A recent study of bimatoprost and bimatoprost free acid (BFA) showed differential effects on matrix metalloprotease (MMP) gene expression, with significant upregulation in MMP1 in trabecular meshwork (TM) cells seen only at “implant levels” of bimatoprost. The preferential effects of high dose bimatoprost on MMP expression on TM cells suggest that increased conventional outflow is due to durable tissue remodeling, underlying long term IOP benefit of implant in some patients, reported researchers at ARVO 2021.

Intracameral bimatoprost SR implant (DURYSTA, Allergan) lowers IOP even after the drug release by the implant ends. Because MMP activity underlies topical bimatoprost effects on IOP, the researchers evaluated if the long-term effects of bimatoprost SR was due to effects of elevated outflow tissue levels of unmetabolized bimatoprost (amide, not BFA) on MMP activity in outflow pathway cells. For the study, human outflow pathway cells in culture were treated with implant tissue levels of bimatoprost (10–1000 µM) or topical tissue levels of BFA (0.1–10 µM). Cells were exposed to drug for 24 hours, and MMP gene expression was measured by PCR array and MMP1 protein by ELISA.

Implant levels of bimatoprost (1000 µM) significantly altered expression of the greatest number of genes in all cell types compared to all other treatments. However, there was noticeable strain to strain differences in responses to implant levels of bimatoprost, they reported.

Reference
Perkumas K, et al.  Differential effects of bimatoprost vs. bimatoprost free acid on outflow cell MMPs. Differential effects of bimatoprost vs. bimatoprost free acid on outflow cell MMPs. Presented at ARVO 2021.