Effects of Latanoprost and Bimatoprost on the Expression of Molecules Relevant to Ocular Inflow and Outflow Pathways

Li, Xiaohong; He, Fenglan; Gabelt, B’Ann T.; Wang, Yun; Cai, Suping; Cao, Juanhui; Fan, Ning; Kaufman, Paul L.; Liu, Xuyang

doi:10.1371/journal.pone.0151644

Cited by 8 publications

(14 citation statements)

References 43 publications

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“…Results are summarized in Figure 3. We also examined the effects of NF-Kbp65 as per Li et al, 13 but we observed no statistically significant differences under any of the described conditions (data not shown).…”

Section: Latanoprost Treatmentsmentioning

confidence: 75%

“…Li et al 13 showed that the treatment of trabecular meshwork cells with latanoprost acid for 5 days caused the amount of fibronectin present in the extracellular matrix of TM1 cells to increase when examined using immunofluorescence. We showed that the treatment of TM1 cells with 10 lM latanoprost for 24 hours caused a statistically significant 1.62-fold increase in the fibronectin expression via qPCR.…”

Section: Discussionmentioning

confidence: 99%

“…Li et al 13 noted that MOLT-3 cells that express the FP receptor show an increase in MMP9 expression upon treatment with latanoprost acid. However, in our study we noted no statistically significant increase in MMP9 expression in the presence of latanoprost.…”

Section: Discussionmentioning

confidence: 99%

“…qPCR analysis was carried out on MMP9 and fibronectin as noted previously. Primers were designed as per Li et al 13 Relative quantities were normalized to HPRT1 (housekeeping gene) and scaled to the scrambled siRNA treated with the vehicle control. Experiments were repeated five times in triplicate.…”

Section: Latanoprost Treatmentmentioning

confidence: 99%

“…We used primers to amplify MMP9, fibronectin, and NFkBp65 as per Li et al 13 to examine the effects of latanoprost on TM1 cells transfected with siRNA for FOXC1. When TM1 cells were treated with 10 lM latanoprost for 24 hours and a control scrambled siRNA, we observed a statistically significant increase in the expression of fibronectin by 1.62-fold (P ¼ 0.006) compared to the scrambled siRNA þ vehicle control.…”

Section: Latanoprost Treatmentsmentioning

confidence: 99%

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FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost

Doucette

Footz

Walter

2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study examines the effect of FOXC1 on the prostaglandin pathway in order to explore FOXC1's role in the prostaglandin-resistant glaucoma phenotype commonly seen in Axenfeld-Rieger syndrome.METHODS. Binding and transcriptional activity of FOXC1 to the gene coding for the EP3 prostaglandin receptor (PTGER3) were evaluated through ChIP-qPCR and luciferase-based assays. Immortalized trabecular meshwork cells (TM1) and HeLa cells had FOXC1 mRNA reduced via siRNA interference. qPCR and Western blot experiments were conducted to examine the changes in prostaglandin receptor expression brought about by lowered FOXC1. TM1 cells were then treated with 10 lM latanoprost acid and/or an siRNA for FOXC1. The expression of fibronectin and matrix metalloproteinase 9 were evaluated via qPCR in each treatment condition.RESULTS. ChIP-qPCR and luciferase experiments confirmed that FOXC1 binds to and activates transcription of the EP3 gene prostaglandin receptor. qPCR and Western experiments in HeLa and TM1 cells showed that FOXC1 siRNA knockdown results in significantly lowered EP3 levels (protein and RNA). In addition, RNA levels of the other prostaglandin receptor genes EP1 (PTGER1), EP2 (PTGER2), EP4 (PTGER4), and FP (PTGFR) were altered when FOXC1 was knocked down in TM1 and HeLa cells. Analysis of fibronectin expression in TM1 cells after treatment with 10 lM latanoprost acid showed a statistically significant increase in expression; this increase was abrogated by cotreatment with a siRNA for FOXC1. CONCLUSIONS.We show the abrogation of latanoprost signalling when FOXC1 is knocked down via siRNA in a trabecular meshwork cell line. We propose that the lower levels of active FOXC1 in Axenfeld-Rieger syndrome patients with glaucoma account for the lack of response to prostaglandin-based medications.Keywords: prostaglandins, Glaucoma, latanoprost, Axenfeld-Rieger, FOXC1 G laucoma is a leading cause of blindness in developed nations and is caused by the death of retinal ganglion cells within the retina. It has been predicted that 79.6 million people will be affected by glaucoma by the year 2020, 10% of whom will be bilaterally blind.1 Risk factors for the development of glaucoma include corticosteroid use, smoking, age, and ethnicity.2 However, the major risk factor for glaucoma is an increase in intraocular pressure (IOP). Generation and maintenance of IOP occurs through aqueous humor (AH) flow. Outflow of AH occurs through two outflow facilities, conventional and uveoscleral, generating this IOP, which maintains the globular structure of the eye. As increased IOP is the major risk factor for developing glaucoma, it is also the primary target for medical intervention. To manage IOP, surgical or pharmaceutical interventions are employed to either increase AH outflow or to decrease the amount of AH produced. The most common treatment for glaucoma is the administration of prostaglandinbased medications to lower IOP through increasing flow via the uveoscleral outflow facility. This outflow occurs through the supraciliary...

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Section: Latanoprost Treatmentsmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Latanoprost Treatmentmentioning

confidence: 99%

Section: Latanoprost Treatmentsmentioning

confidence: 99%

See 3 more Smart Citations

FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost

Doucette

Footz

Walter

2018

Invest. Ophthalmol. Vis. Sci.

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Effect of chronic topical latanoprost on the sclera and lamina cribrosa of form-deprived myopic Guinea pigs

El-Nimri

Yao

Huerta

et al. 2019

Experimental Eye Research

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The purpose of this study was to investigate the effects of latanoprost, an ocular hypotensive prostaglandin analog, on scleral collagen fibers and laminar pores in myopic guinea pigs. Young guinea pigs underwent monocular form deprivation (FD; white plastic diffusers) from 14-days of age for 10-weeks. After the first week, FD eyes also received daily topical A) latanoprost (Lat, 0.005%, n = 5) or B) artificial tears (AT; n = 5). At the end of the treatment period, animals were sacrificed, eyes enucleated and optic nerve heads (ONH) excised to include a 4 mm diameter ring of surrounding sclera for scanning electron microscopy (SEM), and an additional 6 mm ring of sclera surrounding the ONH was excised for transmission electron microscopy (TEM). For SEM, ONH samples were first immersed in 0.2M NaOH for 30 h to isolate the collagenous structures. All samples were stained with osmium tetroxide, dried through an ethanol series and finally subjected to critical point drying before imaging. Image J was used to analyze the dimensions of laminar pores (SEM images) and scleral collagen fibers (TEM images). As previously reported in a related study, latanoprost was effective in inhibiting myopia progression in FD eyes of the guinea pigs. The scleral fibers of FD myopic eyes treated with AT were smaller and more variable in cross-sectional areas compared to untreated (fellow) eyes (mean areas: 0.0059 ± 0.0013 vs. 0.0085 ± 0.002 μm 2 ; p < 0.001), consistent with scleral changes reported for human myopia. In contrast, the scleral fibers of the Lat-treated FD eyes were similar to those of fellow eyes (0.0083 ± 0.002 vs. 0.0078 ± 0.0014 μm 2 ). However, laminar pore size appeared unaffected by either the FD or drug treatments, with no significant difference found between FD eyes and their fellows, for either treatment group. That daily topical latanoprost appeared to protect against myopia-related changes in scleral collagen, rather than exaggerating them, as might be predicted from its known action on the uveoscleral extracellular matrix, lends further support its use for myopia control. In this guinea pig myopia model, the lamina cribrosa appeared unaffected.

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Polymorphism rs11200638 enhanced HtrA1 responsiveness and expression are associated with age-related macular degeneration

Cai

et al. 2021

Eye

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Effects of Latanoprost and Bimatoprost on the Expression of Molecules Relevant to Ocular Inflow and Outflow Pathways

Cited by 8 publications

References 43 publications

FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost

FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost

Effect of chronic topical latanoprost on the sclera and lamina cribrosa of form-deprived myopic Guinea pigs

Polymorphism rs11200638 enhanced HtrA1 responsiveness and expression are associated with age-related macular degeneration

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