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Matrix Metalloproteinases and Glaucoma Treatment.

Publication ,  Journal Article
Weinreb, RN; Robinson, MR; Dibas, M; Stamer, WD
Published in: J Ocul Pharmacol Ther
May 2020

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health and disease. The activity of MMPs is influenced by the expression of MMPs and tissue inhibitors of metalloproteinase (TIMPs). In the eye, MMP-mediated ECM turnover in the juxtacanalicular region of the trabecular meshwork (TM) reduces outflow resistance in the conventional outflow pathway and helps maintain intraocular pressure (IOP) homeostasis. An imbalance in the MMP/TIMP ratio may be involved in the elevated IOP often associated with glaucoma. The prostaglandin analog/prostamide (PGA) class of topical ocular hypotensive medications used in glaucoma treatment reduces IOP by increasing outflow through both conventional and unconventional (uveoscleral) outflow pathways. Evidence from in vivo and in vitro studies using animal models and anterior segment explant and cell cultures indicates that the mechanism of IOP lowering by PGAs involves increased MMP expression in the TM and ciliary body, leading to tissue remodeling that enhances conventional and unconventional outflow. PGA effects on MMP expression are dependent on the identity and concentration of the PGA. An intracameral sustained-release PGA implant (Bimatoprost SR) in development for glaucoma treatment can reduce IOP for many months after expected intraocular drug bioavailability. We hypothesize that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect.

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Published In

J Ocul Pharmacol Ther

DOI

EISSN

1557-7732

Publication Date

May 2020

Volume

36

Issue

4

Start / End Page

208 / 228

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Tissue Inhibitor of Metalloproteinases
  • Prostaglandins, Synthetic
  • Ophthalmology & Optometry
  • Models, Animal
  • Matrix Metalloproteinases
  • Intraocular Pressure
  • Humans
  • Homeostasis
  • Glaucoma
 

Citation

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Weinreb, R. N., Robinson, M. R., Dibas, M., & Stamer, W. D. (2020). Matrix Metalloproteinases and Glaucoma Treatment. J Ocul Pharmacol Ther, 36(4), 208–228. https://doi.org/10.1089/jop.2019.0146
Weinreb, Robert N., Michael R. Robinson, Mohammed Dibas, and W Daniel Stamer. “Matrix Metalloproteinases and Glaucoma Treatment.J Ocul Pharmacol Ther 36, no. 4 (May 2020): 208–28. https://doi.org/10.1089/jop.2019.0146.
Weinreb RN, Robinson MR, Dibas M, Stamer WD. Matrix Metalloproteinases and Glaucoma Treatment. J Ocul Pharmacol Ther. 2020 May;36(4):208–28.
Weinreb, Robert N., et al. “Matrix Metalloproteinases and Glaucoma Treatment.J Ocul Pharmacol Ther, vol. 36, no. 4, May 2020, pp. 208–28. Pubmed, doi:10.1089/jop.2019.0146.
Weinreb RN, Robinson MR, Dibas M, Stamer WD. Matrix Metalloproteinases and Glaucoma Treatment. J Ocul Pharmacol Ther. 2020 May;36(4):208–228.
Journal cover image

Published In

J Ocul Pharmacol Ther

DOI

EISSN

1557-7732

Publication Date

May 2020

Volume

36

Issue

4

Start / End Page

208 / 228

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Tissue Inhibitor of Metalloproteinases
  • Prostaglandins, Synthetic
  • Ophthalmology & Optometry
  • Models, Animal
  • Matrix Metalloproteinases
  • Intraocular Pressure
  • Humans
  • Homeostasis
  • Glaucoma