Hemin Promotes Corneal Allograft Survival Through the Suppression of Macrophage Recruitment and Activation

Dai, Ye; Cheng, Xiaokang; Yu, Jianfeng; Chen, Xiaoqing; Xiao, Yunfeng; Tang, Fen; Li, Yingqi; Wan, Shangtao; Su, Wenru; Liang, Dan

doi:10.1167/iovs.17-23327

Cited by 10 publications

(9 citation statements)

References 39 publications

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“…[20][21][22] Recent studies indicated that corneal macrophages are critical for corneal wound repair and inflammation. [23][24][25] However, the roles of the corneal macrophages of LCD patients in elimination of the amyloid TGFBIp remain unknown.…”

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confidence: 99%

Impaired Autophagic Degradation of Transforming Growth Factor-β-Induced Protein by Macrophages in Lattice Corneal Dystrophy

Han

Zhang

Lin

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Lattice corneal dystrophy (LCD) is related to the denaturation of transforming growth factor-b-induced protein (TGFBIp). Autophagic degradation of the denatured proteins by macrophages is one pathway to remove the denatured proteins. Thus, we investigated the role of autophagy in the degradation of mutant (MU) TGFBIp in macrophages. METHODS.Corneas from participants were observed by slit-lamp photography and subjected to histopathologic and genetic analysis. Wild-type (WT) and MU TGFBIp were recombined and expressed. Macrophages from MU participants were isolated and cocultured with the recombinant TGFBIp. Colocalization of the two molecules was observed by immunofluorescent microscopy. Enzyme-linked immunosorbent assay, Western blotting, and flow cytometry were used to detect changes in molecule expression related to the phenotype and autophagy process.RESULTS. Fourteen members from a family of 25 were identified as LCD sufferers. Significant TGFBIp aggregates and macrophage infiltration were found only in the corneas of LCD sufferers. Marker accumulation of TGFBIp was found in macrophages exposed to MU TGFBIp even at 5 hours after MU TGFBIp was withdrawn. High expressions of CD68 and CD36 were found in macrophages exposed to WT TGFBIp, but not to MU TGFBIp. Impaired autophagic flux due to defective autophagosome fusion to lysosomes was found in macrophages exposed to MU TGFBIp. Blockage of the autophagic process suppressed the expression of CD68 and CD36 in macrophages exposed to WT TGFBIp to levels similar to those found in macrophages exposed to MU TGFBIp. CONCLUSIONS.Our results suggested that reversion of the defective autophagic process in macrophages may be a therapeutic strategy for patients with LCD.

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confidence: 99%

Impaired Autophagic Degradation of Transforming Growth Factor-β-Induced Protein by Macrophages in Lattice Corneal Dystrophy

Han

Zhang

Lin

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…Our previous study proved that IL-27Rα was up-regulated in CD4 + T cell-mediated allorejection. Data reported that CD4 + T cells and macrophages could directly result in allogeneic graft rejection [10,16,40,41]. Considering that allogeneic grafts have severe inflammatory infiltration, such as CD4 + T cells and macrophages, we postulated that IL-27Rα may act as a targeted biomarker to monitor acute allogeneic graft rejection, based on graft inflammatory cell infiltration, non-invasively and visually.…”

Section: Discussionmentioning

confidence: 98%

IL-27Rα: A Novel Molecular Imaging Marker for Allograft Rejection

Zhao

Shi

et al. 2020

IJMS

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Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27Rα was up-regulated in alloreactive CD4+ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27Rα could be used in monitoring allogeneic graft rejection both in vitro and in vivo. Allogeneic (C57BL/6 donor to BALB/c recipient) and syngeneic (BALB/c both as donor and recipient) skin grafted mouse models were established. The expression of IL-27Rα in grafts was detected. The radio-probe, 125I-anti-IL-27Rα mAb, was prepared. Dynamic whole-body phosphor-autoradiography, ex vivo biodistribution and immunofluorescence staining were performed. The results showed that the highest expression of IL-27Rα was detected in allogeneic grafts on day 10 post transplantation (top period of allorejection). 125I-anti-IL-27Rα mAb was successfully prepared with higher specificity and affinity. Whole-body phosphor-autoradiography showed higher radioactivity accumulation in allogeneic grafts than syngeneic grafts on day 10. The uptake of 125I-anti-IL-27Rα mAb in allogeneic grafts could be almost totally blocked by pre-injection with excess unlabeled anti-IL-27Rα mAb. Interestingly, we found that 125I-anti-IL-27Rα mAb accumulated in allogeneic grafts, along with weaker inflammation earlier on day 6. The high uptake of 125I-anti-IL-27Rα mAb was correlated with the higher infiltrated IL-27Rα positive cells (CD3+/CD68+) in allogeneic grafts. In conclusion, IL-27Rα may be a novel molecular imaging marker to predict allorejection.

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“…Several studies with different cellular injury models have shown that hemin can suppress ROS production via enhancing HO-1 expression. 67,68 FIGURE 9. (A) The electrodes of the MEA were classified into three categories according to their distance to the optic nerve head.…”

Section: Discussionmentioning

confidence: 99%

CoPP-Induced-Induced HO-1 Overexpression Alleviates Photoreceptor Degeneration With Rapid Dynamics: A Therapeutic Molecular Against Retinopathy

Tao

Cai

Zhou

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Retinitis pigmentosa (RP) causes progressive photoreceptor degeneration in the retina. The N-methyl-N-nitrosourea (MNU)-administered mouse is used as a chemically induced RP model with rapid progression rate. This study was designed to study heme oxygenase-1 (HO-1) expression in the MNU-administered mice, and to explore the therapeutic effects of cobalt protoporphyrin (CoPP). METHODS. The HO-1 expression in the retina of MNU-administered mice was analyzed. CoPP was injected intravenously into the MNU-administered mice. Subsequently, the CoPP-treated mice were subjected to functional and morphologic examinations. RESULTS. HO-1 was involved in the MNU-induced photoreceptor degeneration. CoPP treatment enhanced retinal HO-1 expression in the MNU-administered mice. Electroretinogram (ERG) examination and behavioral tests showed that CoPP treatment improved the retinal responsiveness of MNU-administered mice. Histologic analysis and optical coherence tomography (OCT) examination showed that retinal architecture of the CoPP-treated mice was more intact than that of the MNUþvehicle group. Cone photoreceptors in the MNUadministered mice were rescued efficiently by CoPP treatment. Furthermore, multielectrode array (MEA) recording showed that CoPP treatment mitigated the spontaneous firing response, enhanced the light-induced firing response, and preserved the basic configurations of visual signal pathway in the MNU-administered mice. Mechanism studies suggested that CoPP afforded these therapeutic effects by modulating the apoptosis cascades and alleviating the oxidative stress in degenerative retinas. CONCLUSIONS. CoPP alleviated photoreceptor degeneration and rectified the signaling abnormities in MNU-administered mice. CoPP may serve as a potential medication against degenerative retinopathy.

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Hemin Promotes Corneal Allograft Survival Through the Suppression of Macrophage Recruitment and Activation

Abstract: Our results are the first to demonstrate that hemin, a Food and Drug Administration-approved drug, promotes corneal allograft survival. These findings indicate that hemin might be a potential alternative treatment for CGR.

Cited by 10 publications

References 39 publications

Impaired Autophagic Degradation of Transforming Growth Factor-β-Induced Protein by Macrophages in Lattice Corneal Dystrophy

Impaired Autophagic Degradation of Transforming Growth Factor-β-Induced Protein by Macrophages in Lattice Corneal Dystrophy

IL-27Rα: A Novel Molecular Imaging Marker for Allograft Rejection

CoPP-Induced-Induced HO-1 Overexpression Alleviates Photoreceptor Degeneration With Rapid Dynamics: A Therapeutic Molecular Against Retinopathy

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