Synthesis pattern of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) in human explant organ cultures after treatment with latanoprost and dexamethasone

Abstract

We detected a profound upregulation of both MMP-3 and MMP-9 and a mild induction of MMP-2 through latanoprost in the ciliary body, but not the trabecular meshwork or RPE cells. Corticosteroids, on the other hand, downregulated MMP expression in both tissues. This inhibiting effect of corticosteroids on MMP production was reversed by latanoprost.

Endogenous bioactive lipids and the regulation of conventional outflow facility

“…Bioactive agents, laser treatments, and mechanical stress all have effects on endogenous PG synthesis. For example, epinephrine and laser treatment elevate endogenous PG levels in the aqueous humor, while dexamethasone reduces endogenous prostaglandin biosynthesis [42,43]. This is significant because in some people (particularly those with POAG), corticosteroid treatment such as with dexamethasone results in elevated IOP.…”

Dexamethasone Increases Pigment Epithelium-Derived Factor in Perfused Human Eyes

“…3 These results show that the PEDF increase was accompanied by a decrease in gelatinolytic activities (92-kDa zymogen).…”

“…4 It is rich in collagens, glycosaminoglycans, and proteoglycans, and contains proteinases, including matrix metalloproteinases (MMPs). 3,15 MMPs, involved in ECM remodeling, are known to directly influence the resistance of the TM to aqueous humor outflow and subsequently affect IOP. 15 Of the MMPs MMP-2 and MMP-9 degrade PEDF and abolish its activities, 12 thus contributing to its likely turnover.…”

“…Interestingly, DEX downregulates MMPs 3 ( Fig. 5) and upregulates protease inhibitors (TIMPs), 3,6 eliciting an overall inhibition of proteolysis in the TM. Thus, the DEX-induced increase of PEDF seen here is not only the result of a transcriptional upregulation, but also of an upregulation at the post-translation level caused by the inhibition of its degradation enzymes.…”

“…Although dexamethasone (DEX) is frequently used to treat inflammation, its administration can adversely cause IOP elevation and glaucoma. 2 One mechanism by which DEX induces elevated IOP includes an increase in ECM deposition in the TM, 3,4 which would in part cause increased resistance to aqueous humor outflow. However, not all molecular mediators for this process have been elucidated.…”