Rituximab Attenuated Lipopolysaccharide-Induced Oxidative Cytotoxicity, Apoptosis, and Inflammation in the Human Retina Cells via Modulating the TRPM2 Signaling Pathways

ABSTRACT

Purpose

We investigated the possible protective effects of rituximab (RTX) on LPS-induced oxidant, inflammatory, and apoptotic adverse actions via the inhibition of TRPM2 channel in the adult retinal pigment epithelial-19 (ARPE-19) cells.

Methods

In the cultured ARPE-19 cells, we induced five main groups as control, RTX (10 μg/ml), LPS (1 μg/ml), LPS+RTX, and LPS+TRPM2 blockers (ACA or 2/APB).

Results

The levels of apoptosis, cell death, mitochondrial free reactive oxygen radicals (mitROS), cytosolic ROS, lipid peroxidation, caspase −3, caspase −8, caspase −9, ADP-ribose-induced TRPM2 current density, TNF-α, IL-1β, cytosolic free Zn²⁺, and Ca²⁺ were increased by LPS, although their levels were diminished by the treatments of RTX and TRPM2 blockers.

Conclusions

The LPS-induced mitROS, inflammatory cytokine, and apoptosis levels were modulated via TRPM2 inhibition in the human retinal epithelial cells by the RTX treatment. The RTX may be considered as a new therapeutic approach to LPS-induced human retinal epithelial cell injury.

KEYWORDS:

• Apoptosis
• ARPE-19 cells
• human retina cells
• lipopolysaccharide
• oxidative stress
• rituximab
• TRPM2 channel

List of abbreviations

Table

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data

The dataset and analyses were generated in the BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture and Industry Ltd (Isparta, Turkey), and they are available from the corresponding author on reasonable request.

Authors’ contributions

Both authors equally contributed to the study conception and design. The assays were done by Mustafa Nazıroğlu. Data analysis was done by Hatice Daldal. After preparing the draft manuscript by Mustafa Nazıroğlu, its revision was performed by both authors.

Ethical approval

There is no human and animal participants or samples in the current study.

Additional information

Funding

The current study was carried out with financial support from a company (BSN Health) (Project No: 2021-06. Project owner: Dr. Hatice Daldal).