MIF promoter polymorphisms are associated with epiretinal membrane but not retinal detachment with PVR in an american population

Cebulla, Colleen M.; Stevenson, William; Law, Heather Van; Heisler-Taylor, Tyler; Hamadmad, Sumaya; Shah, Manisha; Kim, Bongsu; Davidorf, Frederick H.; Ohr, Matthew; Wells, Michael B.; Yanoga, Fatoumata; Chang, Susie; Terrell, William; Miller, Daniel M.; Klisovic, Dino D.; Allen, J. R. L.; Shah, Neelima; Geraymovych, Elena; Tarabishy, Ahmad B.; Kondapalli, Srinivas Sai A; Brewington, Beatrice Y.; Inman, Andrea; Williams, Demarcus; Kusibati, Rania; Mathias, Jay; Yildiz, Vedat; Fernández, Soledad; Wisely, C. Ellis; Pilarski, Robert; Abdel‐Rahman, Mohamed H.

doi:10.1016/j.exer.2019.05.007

Cited by 5 publications

(2 citation statements)

References 40 publications

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“…It was demonstrated i n vitro that transient exposure of fibroblasts to MIF induced fibroblast activation and promoted fibroblast proliferation, migration and replenishment of cell monolayers after scratching (59). In a recent study, an interesting genetic association of MIF with epiretinal membrane formation was found, suggesting a potential contribution of MIF to formation of the membranes (60).…”

Section: Discussionmentioning

confidence: 99%

The Proinflammatory and Proangiogenic Macrophage Migration Inhibitory Factor Is a Potential Regulator in Proliferative Diabetic Retinopathy

et al. 2019

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The macrophage migration inhibitory factor (MIF)/CD74 signaling pathway is strongly implicated in inflammation and angiogenesis. We investigated the expression of MIF and its receptor CD74 in proliferative diabetic retinopathy (PDR) to reveal a possible role of this pathway in the pathogenesis of PDR. Levels of MIF, soluble (s)CD74, soluble intercellular adhesion molecule-1 (sICAM-1) and vascular endothelial growth factor (VEGF) were significantly increased in the vitreous from patients with PDR compared to nondiabetic control samples. We detected significant positive correlations between the levels of MIF and the levels of sICAM-1 (r = 0.43; p = 0.001) and VEGF (r = 0.7; p < 0.001). Through immunohistochemical analysis of PDR epiretinal membranes, significant positive correlations were also found between microvessel density (CD31 expression) and the numbers of blood vessels expressing MIF (r = 0.56; p = 0.045) and stromal cells expressing MIF (r = 0.79; p = 0.001) and CD74 (r = 0.59; p = 0.045). Similar to VEGF, MIF was induced in Müller cells cultured under hypoxic conditions and MIF induced phosphorylation of ERK1/2 and VEGF production in Müller cells. Intravitreal administration of MIF in normal rats induced increased retinal vascular permeability and significant upregulation of phospho-ERK1/2, NF-κB, ICAM-1 and vascular cell adhesion molecule-1 expression in the retina. MIF induced migration and proliferation of human retinal microvascular endothelial cells. These results suggest that MIF/CD74 signaling is involved in PDR angiogenesis.

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Section: Discussionmentioning

confidence: 99%

The Proinflammatory and Proangiogenic Macrophage Migration Inhibitory Factor Is a Potential Regulator in Proliferative Diabetic Retinopathy

et al. 2019

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“…We have shown that MIF inhibition is anti-gliotic and neuroprotective to photoreceptors in a murine retinal detachment (RD) model (Kim et al, 2017a). Moreover, our lab identified a human genetic association of MIF promoter polymorphisms with epiretinal membrane (ERM) formation (Cebulla et al, 2019). MG are the predominant components of ERM, suggesting that MIF could play an important role in the pathological function of retinal glia (Matsuda, Tagawa, Yoshida, Matsuda, & Nishihira, 1997).…”

Section: Introductionmentioning

confidence: 99%

Ibudilast Protects Retinal Bipolar Cells from Excitotoxic Retinal Damage and Activates the mTOR Pathway

Hamadmad,

Heisler-Taylor,

Goswami

et al. 2024

Preprint

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Ibudilast, an inhibitor of macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE), has been recently shown to have neuroprotective effects in a variety of neurologic diseases. We utilize a chick excitotoxic retinal damage model to investigate ibudilast's potential to protect retinal neurons. Using single cell RNA-sequencing (scRNA-seq), we find that MIF, putative MIF receptors CD74 and CD44, and several PDEs are upregulated in different retinal cells during damage. Intravitreal ibudilast is well tolerated in the eye and causes no evidence of toxicity. Ibudilast effectively protects neurons in the inner nuclear layer from NMDA-induced cell death, restores retinal layer thickness on spectral domain optical coherence tomography, and preserves retinal neuron function, particularly for the ON bipolar cells, as assessed by electroretinography. PDE inhibition seems essential for ibudilast's neuroprotection, as AV1013, the analogue that lacks PDE inhibitor activity, is ineffective. scRNA-seq analysis reveals upregulation of multiple signaling pathways, including mTOR, in damaged Müller glia (MG) with ibudilast treatment compared to AV1013. Components of mTORC1 and mTORC2 are upregulated in both bipolar cells and MG with ibudilast. The mTOR inhibitor rapamycin blocked accumulation of pS6 but did not reduce TUNEL positive dying cells. Additionally, through ligand-receptor interaction analysis, crosstalk between bipolar cells and MG may be important for neuroprotection. We have identified several paracrine signaling pathways that are known to contribute to cell survival and neuroprotection and might play essential roles in ibudilast function. These findings highlight ibudilast's potential to protect inner retinal neurons during damage and show promise for future clinical translation.

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MIF in the cerebrospinal fluid is decreased during relapsing-remitting while increased in secondary progressive multiple sclerosis

Hjæresen

Sejbæk

Axelsson

et al. 2022

Journal of the Neurological Sciences

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MIF promoter polymorphisms are associated with epiretinal membrane but not retinal detachment with PVR in an american population

Cited by 5 publications

References 40 publications

The Proinflammatory and Proangiogenic Macrophage Migration Inhibitory Factor Is a Potential Regulator in Proliferative Diabetic Retinopathy

The Proinflammatory and Proangiogenic Macrophage Migration Inhibitory Factor Is a Potential Regulator in Proliferative Diabetic Retinopathy

Ibudilast Protects Retinal Bipolar Cells from Excitotoxic Retinal Damage and Activates the mTOR Pathway

MIF in the cerebrospinal fluid is decreased during relapsing-remitting while increased in secondary progressive multiple sclerosis

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