Tumor necrosis factor-alpha regulates photoreceptor cell autophagy after retinal detachment

Abstract

Photoreceptor cell death is the ultimate process underlying many retinal diseases, including retinal detachment (RD). Both autophagy and inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), participate in photoreceptor cell death after RD. In this study, we examined whether TNF-α inhibition would impact the autophagy of photoreceptors and reduce the death of photoreceptors after retinal detachment (RD). RD models were created in C57BL/6J mice by a subretinal injection of 1% hyaluronic acid. The TNF-α inhibitor infliximab was administered via intraperitoneal injection two hours before RD. The levels of TNF-α and the autophagy-related proteins Atg5 and LC3B were assayed by immunofluorescence at 1 day, 3 days, and 7 days following RD. Apoptosis was examined at 3 days post-detachment via TUNEL assays. Photoreceptor cell counts were assessed at 7 days after RD. After RD, the protein levels of LC3B and Atg5 increased and reached a peak at 3 days, which decreased at 7 days. The expression of LC3B and Atg5 was prolonged and increased at a slower rate with TNF-α inhibition. The moderate augmentation and extension of autophagy through TNF-α inhibition resulted in the reduction of apoptosis and the enhancement of photoreceptor cell survival.

Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions

“…40 When prolonged and augmented by calpain or TNF-α inhibitor, autophagy could significantly reduce photoreceptor apoptosis and protect retina. 38,41 In our in vitro study, autophagy in 661w cells was induced under hypoxic conditions, which was consistent with previous researches of others, 24 and inhibiting autophagy with 3-MA resulted in more apoptotic cells.…”

“…In an RD model, autophagy peaked at 3 days and decreased at 7 days after RPE‐photoreceptor separation was induced, and played a role in regulating the level of photoreceptor apoptosis in a Fas‐dependent way . When prolonged and augmented by calpain or TNF‐α inhibitor, autophagy could significantly reduce photoreceptor apoptosis and protect retina . In our in vitro study, autophagy in 661w cells was induced under hypoxic conditions, which was consistent with previous researches of others, and inhibiting autophagy with 3‐MA resulted in more apoptotic cells.…”

Microglia inhibit photoreceptor cell death and regulate immune cell infiltration in response to retinal detachment

“…This indicates that the ERG recordings obtained in this murine RD model originate predominately from nondetached areas and that the amplitudes would be reflective of the size/function of the nondetached retina, not the area of detachment. Although many reports demonstrate photoreceptor cell death in murine models of sodium hyaluronate-induced RD, ERG data were not presented in these reports ( 11 , 54 – 57 ).…”

Double agents of cell death: novel emerging functions of apoptotic regulators

“…3). Inhibition of the inflammatory factor and death receptor ligand TNF resulted in protection of photoreceptors after retinal detachment, presumably due to a transient increase in autophagy and a corresponding reduction in apoptosis [75]. Antiapoptotic BCL-2 proteins also bind to the autophagy protein Beclin 1, preventing it from interacting with the VPS34 PI3K complex responsible for autophagy initiation [76][77][78].…”