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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-?), participate in photoreceptor cell death after RD. In this study, we examined whether TNF-? 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-? inhibitor infliximab was administered via intraperitoneal injection two hours before RD. The levels of TNF-? 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-? inhibition. The moderate augmentation and extension of autophagy through TNF-? inhibition resulted in the reduction of apoptosis and the enhancement of photoreceptor cell survival.

SUBMITTER: Xie J

PROVIDER: S-EPMC5719449 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Xie Jia J Zhu Ruilin R Peng Yuan Y Gao Wenna W Du Jiantong J Zhao Liang L Chi Ying Y Yang Liu L

Scientific reports 20171207 1

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% hyaluro ...[more]

PMID: 29215050

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Project description:Retinal detachment (RD) occurs in several major retinal conditions and often causes irreversible vision loss due to photoreceptor cell death. Retinal residential microglial cells are activated following RD and participate in photoreceptor cell death via direct phagocytosis and the regulation of inflammatory responses. Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor exclusively expressed on microglial cells in the retina, and has been reported to affect microglial cell homeostasis, phagocytosis and inflammatory responses in the brain. In this study, increased expression of multiple cytokines and chemokines in the neural retina was observed starting at 3 h following RD. Trem2 knockout (Trem2-/-) mice exhibited significantly more photoreceptor cell death than wild-type controls at 3 days after RD, and the number of TUNEL positive photoreceptor cells progressively decreased from day 3 to day 7 post-RD. A significant thinning of the outer nuclear layer (ONL), with multiple folds was observed in the Trem2-/- mice at 3 days post-RD. Trem2 deficiency reduced microglial cell infiltration and phagocytosis of stressed photoreceptors. There were more neutrophils in Trem2-/- retina following RD than in controls. Using purified microglial cells, we found Trem2 knockout is associated with increased CXCL12 expression. The aggravated photoreceptor cell death was largely reversed by blocking the CXCL12-CXCR4 mediated chemotaxis in Trem2-/- mice after RD. Our findings suggested that retinal microglia are protective in preventing further photoreceptor cell death following RD by phagocytosing presumably stressed photoreceptor cells and by regulating inflammatory responses. TREM2 is largely responsible for such protective effect and CXCL12 plays an important role in regulating neutrophil infiltration after RD. Collectively, our study pinpointed TREM2 as a potential target of microglial cells to ameliorate RD-induced photoreceptor cell death.

Dataset Information

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

Publications

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

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