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Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant.

Publication ,  Journal Article
Stamer, WD; Perkumas, KM; Kang, MH; Dibas, M; Robinson, MR; Rhee, DJ
Published in: Invest Ophthalmol Vis Sci
March 1, 2023

PURPOSE: The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix metalloproteinase (MMP) gene expression in cells from human aqueous outflow tissues. METHODS: MMP gene expression by human trabecular meshwork (TM), scleral fibroblast (SF), and ciliary muscle (CM) cells exposed to 10 to 1000 µM bimatoprost or 0.1 to 10 µM BFA (intraocular concentrations after intracameral bimatoprost implant and topical bimatoprost dosing, respectively) was measured by polymerase chain reaction array. RESULTS: Bimatoprost dose-dependently upregulated MMP1 and MMP14 mRNA in all cell types and MMP10 and MMP11 mRNA in TM and CM cells; in TM cells from normal eyes, mean MMP1 mRNA levels were 62.9-fold control levels at 1000 µM bimatoprost. BFA upregulated MMP1 mRNA only in TM and SF cells, to two- to three-fold control levels. The largest changes in extracellular matrix (ECM)-related gene expression by TM cells derived from normal (n = 6) or primary open-angle glaucoma (n = 3) eyes occurred with 1000 µM bimatoprost (statistically significant, ≥50% change for 9-11 of 84 genes on the array, versus 1 gene with 10 µM BFA). CONCLUSIONS: Bimatoprost and BFA had differential effects on MMP/ECM gene expression. Dramatic upregulation in MMP1 and downregulation of fibronectin, which occurred only with bimatoprost at high concentrations observed in bimatoprost implant-treated eyes, may promote sustained outflow tissue remodeling and long-term intraocular pressure reduction beyond the duration of intraocular drug bioavailability. Variability in bimatoprost-stimulated MMP upregulation among cell strains from different donors may help explain differential long-term responses of patients to bimatoprost implant.

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Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

March 1, 2023

Volume

64

Issue

3

Start / End Page

15

Location

United States

Related Subject Headings

  • Tonometry, Ocular
  • Sclera
  • Ophthalmology & Optometry
  • Matrix Metalloproteinase 1
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Bimatoprost
  • 3212 Ophthalmology and optometry
  • 11 Medical and Health Sciences
 

Citation

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MLA
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Stamer, W. D., Perkumas, K. M., Kang, M. H., Dibas, M., Robinson, M. R., & Rhee, D. J. (2023). Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant. Invest Ophthalmol Vis Sci, 64(3), 15. https://doi.org/10.1167/iovs.64.3.15
Stamer, W Daniel, Kristin M. Perkumas, Min H. Kang, Mohammed Dibas, Michael R. Robinson, and Douglas J. Rhee. “Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant.Invest Ophthalmol Vis Sci 64, no. 3 (March 1, 2023): 15. https://doi.org/10.1167/iovs.64.3.15.
Stamer WD, Perkumas KM, Kang MH, Dibas M, Robinson MR, Rhee DJ. Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant. Invest Ophthalmol Vis Sci. 2023 Mar 1;64(3):15.
Stamer, W. Daniel, et al. “Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant.Invest Ophthalmol Vis Sci, vol. 64, no. 3, Mar. 2023, p. 15. Pubmed, doi:10.1167/iovs.64.3.15.
Stamer WD, Perkumas KM, Kang MH, Dibas M, Robinson MR, Rhee DJ. Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant. Invest Ophthalmol Vis Sci. 2023 Mar 1;64(3):15.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

March 1, 2023

Volume

64

Issue

3

Start / End Page

15

Location

United States

Related Subject Headings

  • Tonometry, Ocular
  • Sclera
  • Ophthalmology & Optometry
  • Matrix Metalloproteinase 1
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Bimatoprost
  • 3212 Ophthalmology and optometry
  • 11 Medical and Health Sciences