How Prostaglandin Analogues and the PTGFR do the (PRESTO-) Tango

Theme: Glaucoma
What: Glaucoma
Part of: Glaucoma I: Medical / Glaucome I: Médical
When: 5/31/2024, 11:15 AM - 12:45 PM
Where: Room | Salle 801

Abstract

Purpose: The current first-line treatment for glaucoma are prostaglandin analogues (PGAs). These mimic the interaction between the Prostaglandin F2alpha molecule (PGF2α) and the Prostaglandin F receptor (PTGFR). The PTGFR is located on trabecular meshwork cells and when activated, increases the outflow of aqueous humour from the eye to lower intraocular pressure.

There is currently a gap in the literature regarding the exact molecular interaction between PGAs and the PTGFR. Directly treating trabecular meshwork cells with PGAs for example, does not account for pleiotropic downstream cellular effects such as proliferation and differentiation, making data difficult to interpret. Moreover, there remains a need for improved efficacy and adjuvant therapies to enhance our therapeutic index of glaucoma treatments.

Our study aimed to observe the interaction between various PGAs and the PTGFR in an isolated cell culture model using a modified PRESTO-Tango reporter assay developed by Kroeze and colleagues (2015). This provides a measurable luminescence response equal to receptor-ligand interaction, allowing a better definition of their interactions and determination of which PGA concentrations caused the greatest receptor activation.

Study Design: Basic science study

Methods: HTLA cells were transfected with the PTGFR-Tango plasmid and treated with increasing doses (0.1μM, 1μM, and 10μM) of Latanoprost, Monoprost, Travoprost, and Bimatoprost. HTLA cells were treated with PGF2α as a positive control, and the synthetic antagonist AL-8810 as a negative control. Luminescence readings were obtained via Bright-Glo Luciferase Assay.

Results: The 0.1μM Latanoprost and Monoprost treatments were found to have the greatest receptor activation from the concentrations tested, with 14.50% and 9.99% (p<0.05) receptor activation, respectively. The 1μM Travoprost treatment was found to have the greatest PTGFR activation from the concentrations tested with 76.53% (p<0.05) receptor activation. As expected, the Bimatoprost treatments did not yield a significant response, likely due to its prostamide activity reported in the literature.

Conclusions: We have established a working model to compare and standardize the receptor activation response of existing PGAs with the PTGFR. This holds the potential for future work to screen possible adjuvant therapies, as well as discover new drugs to further improve glaucoma management.

Presenter(s)

Presenting Author: Nicole Costanzo

Additional Author(s):

Nicholas Bel, Lakehead University

Neelam Khaper, Northern Ontario School of Medicine University

Sanjoy Gupta, Northern Ontario School of Medicine University

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