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Infliximab Shows Promise in Treating Retinal Disorders

Article

A recent study examined whether the use of the anti–tumor necrosis factor agent infliximab could reduce the death of photoreceptors after retinal detachment in an experimental mouse model.

Tumor necrosis factor-alpha (TNF-a) participates in photoreceptor cell death, a process involved in many retinal diseases, including retinal detachment (RD), that can cause irreversible visual impairment and blindness. The death of photoreceptor cells begins immediately after RD, peaking at 2 to 3 days after RD. A recent study, published in Scientific Reports, examined whether the use of the anti-TNF agent infliximab could reduce the death of photoreceptors after RD in an experimental mouse model.

First, the researchers induced RD in adult male mice, and detected the expression of the TNF-a protein in the retina at 1 day, 3 days, and 7 days after RD using Western blotting and immunofluorescence testing. Analysis showed that the expression of TNF-a in the retina peaked in photoreceptor cells at 1 day after RD.

Next, the researchers investigated the effects of the anti-TNF agent infliximab on the expression of TNF-a following RD. The investigators injected infliximab (5 mg/kg) intraperitoneally 2 hours before RD induction, and injected saline into controls. Retinas were harvested and sectioned at 1 day following RD. The researchers found that the expression of TNF-a was suppressed after RD in the infliximab-treated retinas compared with the control retinas at days 1, 3, and 7.

Additionally, the investigators sought to better understand whether infliximab could regulate autophagy, which plays a dual role in cell death and cell survival, by examining the impact of infliximab on the activity of 2 proteins associated with autophagy: LC3B and Atg5. The researchers found that, with infliximab treatment, increased expression of LC3B was maintained through 7 days after RD, while the level of LC3B decreased to baseline at 7 days after RD without infliximab. Similarly, expression of Atg5 increased at day 1 to day 3, and its expression was sustained at 7 days with infliximab. Atg5 levels also declined to baseline at 7 days following RD in controls.

To examine whether this prolonged autophagy caused by inhibiting TNF-a with infliximab led to increased cell survival in photoreceptors, the researchers investigated photoreceptor cell survival at 7 days after RD with infliximab, and found that, with infliximab treatment, there was not a decrease in the number of photoreceptor cells in the outer nuclear layer of the retina, compared with a 40% to 50% loss of such cells in retinas not treated with infliximab.

The researchers concluded that TNF-a is a critical regulator of autophagy that is correlated closely to the homeostasis of photoreceptor cells in this experimental mouse model.

“Autophagy was thought to have a complex influence on cell death and cell survival. We proved that the appropriate level of autophagy activity had a critical influence on the augmentation of cell survival,” the authors concluded. "Control of autophagy to a proper level under pathological conditions may provide a new therapeutic approach to treat photoreceptor degeneration in retinal disorders."

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