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Effect of adalimumab as an anti-inflammatory agent on gene expression of retinal pigment epithelial cells - 27/04/24

Doi : 10.1016/j.biopha.2024.116568 
M. Hossein Nowroozzadeh , Mojtaba Yousefi , Mostafa Abuali , Fatemeh Sanie-Jahromi
 Poostchi Ophthalmology Research Center, Department of Ophthalmology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran 

Correspondence to: Poostchi Ophthalmology Research Center, Zand Boulevard, Poostchi Street, Shiraz, Islamic Republic of Iran.Poostchi Ophthalmology Research CenterZand Boulevard, Poostchi StreetShirazIslamic Republic of Iran

Abstract

Adalimumab (ADA) is an anti-inflammatory antibody that has FDA approval as a systemic medication for treating noninfectious uveitis. It is also provisionally being investigated as an intravitreal injection for various retinal conditions. This study aimed to assess the effect of ADA on apoptotic, inflammatory, and fibrogenesis gene expression at mRNA and protein levels in retinal pigment epithelial (RPE) cells. RPEs were treated with serial concentrations of ADA (0.5x, x, 2x, and 4x; [x = 250 µg/mL]) for 24 hours. MTT assay was done and the mRNA and protein expressions were quantified using real-time PCR and ELISA assay, respectively. The mRNA levels of IL-1b and IL-6 were significantly increased in ADA-treated RPEs at 0.5x and x concentrations. However, the increase in cytokine secretion was observed only in IL-1b at x concentration. TGF-β was significantly upregulated in the 0.5x and 4x doses of ADA both at mRNA and protein levels. MTT assay, along with an unchanged BCL-2/BAX ratio confirmed the safety of ADA on RPEs at all studied concentrations. In conclusion, despite its safety, the 2x concentration of ADA was the only dose that did not ignite the expression of any of the studied inflammatory and fibrogenesis genes. This dosage, which is roughly equal to 2 mg intravitreal dose in a clinical setting, might be referred to as a reference starting point for future in-vivo studies in ocular conditions.

El texto completo de este artículo está disponible en PDF.

Highlights

ADA is an FDA-approved biological drug that has been used successfully in many inflammatory disorders including uveitis.
There are reports of the adverse effects of ADA including exacerbation of inflammation when applied in clinical trials.
Our study showed upregulation of IL-1b and IL-6 at 0.5x and x concentrations, and upregulation of TGF-β at 0.5x and 4x dose.
ADA may trigger inflammation and EMT when directly applied to RPE cells, so its local application may exacerbate PVR.
Intravitreal ADA probably has a narrow therapeutic window, and the 2mg/4mL vitreous may be the safest dose for clinical use.

El texto completo de este artículo está disponible en PDF.

Keywords : Uveitis, Adalimumab, RPE, Apoptosis, Inflammation, Fibrogenesis, EMT


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© 2024  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 174

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