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.
Highlights
Photoreceptor cells play critical roles in the complex neural circuitry of the retina, which is responsible for transducing light signals into a pattern of electrical impulses
We showed that TNF-α was a critical regulator of photoreceptor autophagy that was correlated closely with the homeostasis of photoreceptor cells using an experimental retinal detachment (RD) model in mice
The prolonged and temperate rise of autophagy activity introduced by inhibition of TNF-α expression lead to the elimination of photoreceptor apoptosis and the improvement of photoreceptor cell survival after RD
Summary
Photoreceptor cells play critical roles in the complex neural circuitry of the retina, which is responsible for transducing light signals into a pattern of electrical impulses. The processes of photoreceptor cell death in retinal diseases are still indistinct. Induced RD is an appropriate model to study the mechanisms of photoreceptor cell death and rescue. Accumulating evidence suggests that there are non-apoptosis pathways involved in photoreceptor cell death, such as autophagy[9] and necrosis[10]. Autophagy plays a complex role in photoreceptor cells, both protective and traumatic. As the exploration of autophagy has continued, researchers have found that inflammation plays a critical role in autophagy in other diseases; for example, the autophagy reaction introduced by TNF-α leads to the apoptosis of trophoblastic cells[11]. Autophagy and inflammation may provide a new perspective for the strategy of preventing photoreceptor cell loss in retinal degeneration diseases
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