Gene Expression Profile of Hyperoxic and Hypoxic Retinas in a Mouse Model of Oxygen-Induced Retinopathy

Ishikawa, Keijiro; Yoshida, Shigeo; Kadota, Koji; Nakamura, Takanori; Niiro, Hiroaki; Arakawa, Satoshi; Yoshida, Ayako; Akashi, Koichi; Ishibashi, Tatsuro

doi:10.1167/iovs.09-4605

Cited by 61 publications

(58 citation statements)

References 44 publications

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“…RNA isolation and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were performed as described. 1 The primers were as follows: for Mip-1b, 5 0 -CCATGAAGCTCTGCGTGTCTG-3 0 and 5 0 -GGCTTGGAG CAAAGACTGCTG-3 0 ; for F4/80, 5 0 -CGCTGCTGGTTGA ATACAGAGA-3 0 and 5 0 -CGGTTGAGCAGACAGTGAATG A-3 0 ; for Vegfa, 5 0 -GGAGAGCAGAAGTCCCATGA-3 0 and 5 0 -ACTCCAGGGCTTCATCGTTA-3 0 ; and for GAPDH, 5 0 -GT GAAGGTCGGTGTGAACGG-3 0 and 5 0 -TCTCCATGGTGGT GAAGACA-3 0 .…”

Section: Rna Isolation and Real-time Quantitative Reverse Transcriptimentioning

confidence: 99%

“…Protein was isolated as described. 1 An ELISA kit (R&D Systems, Minneapolis, MN) was used to measure the concentrations of MIP-1b according to the manufacturers' instructions. The minimum concentration of MIP1b that could be detected was 6.0 pg/ml.…”

Section: Enzyme-linked Immunosorbent Assaymentioning

confidence: 99%

“…1 To confirm the upregulation of the mRNA and protein levels of MIP-1b in OIR mice, we performed real-time qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively, on retinal extracts. Real-time qRT-PCR showed that the mRNA of MIP-1b was slightly increased in the retinas of mice 5 days after hyperoxia (P12), and the level increased and peaked at 1 day after hypoxia.…”

Section: Induction Of Mip-1b In Oir Retinasmentioning

confidence: 99%

“…The most upregulated gene among the differentially expressed genes in hypoxic retinas was the macrophage inflammatory protein1b (MIP-1b) and not vascular endothelial growth factor A (VEGF-A) and other chemokines. 1 MIP-1b, also known as chemokine CC motif ligand 4, is a member of the CC chemokine family that are characterized by their ability to direct migration of leukocytes into inflamed tissues. 2 MIP-1b was first isolated from the culture medium of LPS-activated macrophages, 3 and it recruited macrophages/microglia to the sites of injury in patients with arthritis, 4 sepsis, 5 and systemic sclerosis.…”

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confidence: 99%

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Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy

Ishikawa

Nakao

Sassa

et al. 2012

Laboratory Investigation

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Recent clinical observations have indicated that vascular endothelial growth factor (VEGF) is a key factor that stimulates the development of preretinal pathological neovascularization (NV). However, it has not been established how intraretinal physiological revascularization of hypoxic avascular areas is regulated. Our earlier study on the gene expression profile of hypoxic retinas in a mouse model of oxygen-induced retinopathy (OIR) showed that macrophage inflammatory protein-1b (MIP-1b) was the most upregulated protein. The purpose of this study was to investigate the role played by MIP-1b in recruiting bone marrow-derived monocyte lineage cells (BM-MLCs) in a mouse model of OIR. Our results showed that MIP-1b was upregulated, and its receptor, CCR5, was expressed in BM-MLCs in the hypoxic inner retina. Neutralizing Ab against MIP-1b reduced the infiltration of BM-MLCs into the OIR retinas and increased the avascular area and preretinal neovascular tufts. A very strong significant correlation was found between the area of the preretinal neovascular tufts and the avascular area, regardless of the extent of BM-MLC infiltration into the OIR retinas. Additional treatment with VEGF-A-neutralizing Ab showed that the MIP-1b-regulated pathological NV strongly depended on VEGF-A, which was probably secreted by the hypoxic avascular retinas. These results indicate that MIP-1b is involved in the recruitment of BM-MLCs, which have a significant role in the physiological revascularization of hypoxic avascular retinas. Overall, these findings indicate that the MIP-1b induction of BM-MLCs might possibly be used to promote intraretinal revascularization and thus prevent the abnormal NV in ischemic vision-threatening retinal diseases. Tissue hypoxia is believed to be the common mechanism that initiates a series of events leading to compensatory angiogenesis. Hypoxia-induced retinal neovascularization (NV) is the main contributor to proliferative vascular diseases, such as diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. These diseases can lead to irreversible damage to visual function.To determine the factors that are activated during retinal hypoxia, we performed a gene expression profile of hypoxic retinas obtained from a mouse model of oxygen-induced retinopathy (OIR) using gene microarray analyses. The results identified the functional set of genes that are related to the post-ischemic inflammation, neural and vascular development, and subsequent pathological NV. The most upregulated gene among the differentially expressed genes in hypoxic retinas was the macrophage inflammatory protein1b (MIP-1b) and not vascular endothelial growth factor A (VEGF-A) and other chemokines. 1 MIP-1b, also known as chemokine CC motif ligand 4, is a member of the CC chemokine family that are characterized by their ability to direct migration of leukocytes into inflamed tissues. 2 MIP-1b was first isolated from the culture medium of LPS-activated macrophages, 3 and it recruited macrophages/microglia to the sites of...

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Section: Rna Isolation and Real-time Quantitative Reverse Transcriptimentioning

confidence: 99%

Section: Enzyme-linked Immunosorbent Assaymentioning

confidence: 99%

Section: Induction Of Mip-1b In Oir Retinasmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy

Ishikawa

Nakao

Sassa

et al. 2012

Laboratory Investigation

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“…9. RT-PCR analyses of periostin (POSTN), VEGF, VEGFR2, and GAPDH in FVMs derived from patients with proliferative diabetic retinopathy (PDR; lanes [4][5][6][7][8][9][10][11][12][13] and from control retinas (lanes 1-3). After 35 cycles, 8 μL each sample was electrophoresed through a 2% Tris-acetate-EDTA agarose gel, and the fractionated products were stained with ethidium bromide.…”

Section: B Periostinmentioning

confidence: 99%

Fibrovascular Membranes Associated with PDR: Development of Molecular Targets by Global Gene Expression Profiling

Ishikawa¹,

Arima²,

Asato³

et al. 2012

Diabetic Retinopathy

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The immunological link between neonatal lung and eye disease

et al. 2021

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Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are two neonatal diseases of major clinical importance, arising in large part as a consequence of supplemental oxygen therapy used to promote the survival of preterm infants. The presence of coincident inflammation in the lungs and eyes of neonates receiving oxygen therapy indicates that a dysregulated immune response serves as a potential common pathogenic factor for both diseases. This review examines the current state of knowledge of immunological dysregulation in BPD and ROP, identifying similarities in the cellular subsets and inflammatory cytokines that are found in the alveoli and retina during the active phase of these diseases, indicating possible mechanistic overlap. In addition, we highlight gaps in the understanding of whether these responses emerge independently in the lung and retina as a consequence of oxygen exposure or arise because of inflammatory spill‐over from the lung. As BPD and ROP are anatomically distinct, they are often considered discreet disease entities and are therefore treated separately. We propose that an improved understanding of the relationship between BPD and ROP is key to the identification of novel therapeutic targets to treat or prevent both conditions simultaneously.

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Gene Expression Profile of Hyperoxic and Hypoxic Retinas in a Mouse Model of Oxygen-Induced Retinopathy

Abstract: These alterations in gene expression may determine the hyperoxic growth retardation, postischemic inflammation, neovascularization, and remodeling in retinas of murine OIR.

Cited by 61 publications

References 44 publications

Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy

Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy

Fibrovascular Membranes Associated with PDR: Development of Molecular Targets by Global Gene Expression Profiling

The immunological link between neonatal lung and eye disease

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