GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

Ban, Norimitsu; Siegfried, Carla J.; Lin, Jonathan B.; Shui, Ying Bo; Sein, Julia; Pita-Thomas, Wolfgang; Sène, Abdoulaye; Santeford, Andrea; Gordon, Mae O.; Lamb, Rachel; Dong, Zhenyu; Kelly, Shannon C.; Cavalli, Valeria; Yoshino, Jun; Apte, Rajendra S.

doi:10.1172/jci.insight.91455

Cited by 37 publications

(39 citation statements)

References 30 publications

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“…Many biomarkers (eg, troponin, natriuretic peptides, inflammatory markers, coagulation markers, etc) are also predictive of stroke, bleeding, death, HF, hospitalization, 110 and even noncardiovascular conditions such as glaucoma progression (eg, as in the case of growth differentiation factor-15 used in the ABC-bleed score). 111 The performance of biomarker-based scores in real-world clinical practice (outside highly selected trial cohorts) has also been disappointing, 112,113 given that baseline (or near-baseline) determination of biomarkers to predict bleeding risks after many years is bedeviled by the changing clinical risk profile of patient's risks as well as modification of risk factors.…”

Section: Concomitant Medication Predisposing To Bleedingmentioning

confidence: 99%

Antithrombotic Therapy for Atrial Fibrillation

Lip

Banerjee

Boriani

et al. 2018

Chest

721

328

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Section: Concomitant Medication Predisposing To Bleedingmentioning

confidence: 99%

Antithrombotic Therapy for Atrial Fibrillation

Lip

Banerjee

Boriani

et al. 2018

Chest

721

328

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“…Optic nerve crushed was performed as previously described with minor modifications (Ban et al, 2017). Investigator performing the surgery was blinded to the treatments.…”

Section: Rodent Surgeriesmentioning

confidence: 99%

HDAC5 promotes optic nerve regeneration by activating the mTOR pathway

Pita-Thomas

Mahar

Joshi

et al. 2019

Experimental Neurology

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Neurons in the central nervous system (CNS) regenerate poorly compared to their counterparts in the peripheral nervous system. We previously showed that, in peripheral sensory neurons, nuclear HDAC5 inhibits the expression of regenerative associated genes. After nerve injury, HDAC5 is exported to the cytoplasm to promote axon regeneration. Here we investigated the role of HDAC5 in retinal ganglion cells (RGC), a CNS neuron which fails to survive and regenerate axons after injury. In contrast to PNS neurons, we found that HDAC5 is mostly cytoplasmic in naïve RGCs and its localization is not affected by optic nerve injury, suggesting that HDAC5 does not directly suppress regenerative associated genes in these cells. Manipulation of the PKCμ pathway, the canonical pathway that regulates HDAC5 localization in PNS neurons by phosphorylating serine 259 and 498, and other pathways that regulate nuclear/cytoplasmic transport did not affect HDAC5 cytoplasmic localization in RGC. Also, an HDAC5 mutant whose serine 259 and 488 were replaced by alanine (HDAC5 AA) to prevent phosphorylation and nuclear export showed a predominantly cytoplasmic localization, suggesting that HDAC5 resides mostly in the cytoplasm in RGCs. Interestingly, expression of HDAC5 AA , but not HDAC5 wild type, in RGCs in vivo

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“…In fact, primary cultures of human, rat, and bovine ciliary epithelial cells [79], and primary cultures of rat lens epithelial cells have been demonstrated to be capable of producing TGF-B2 [80]. In addition, following RGC death induced by optic nerve crush in mice and rats, tgfb2 gene expression was not significantly increased in the eye, when compared to sham-operated eyes [81]. Furthermore, TGF-B2 concentrations in AH did not correlate with the severity of glaucomatous neurodegeneration in a cross-sectional human study that compared various stages of disease severity in primary open angle glaucoma patients [81].…”

Section: Molecular Biomarkers To Monitor Neurodegeneration In Glaucomamentioning

confidence: 99%

“…In addition, following RGC death induced by optic nerve crush in mice and rats, tgfb2 gene expression was not significantly increased in the eye, when compared to sham-operated eyes [81]. Furthermore, TGF-B2 concentrations in AH did not correlate with the severity of glaucomatous neurodegeneration in a cross-sectional human study that compared various stages of disease severity in primary open angle glaucoma patients [81]. Moreover, studies have shown that TGF-B2 concentrations are linked to the decreased ability of the trabecular meshwork to effectively drain AH and maintain IOP at a normal range, leading to elevation of IOP [82].…”

Section: Molecular Biomarkers To Monitor Neurodegeneration In Glaucomamentioning

confidence: 99%

Monitoring Neurodegeneration in Glaucoma: Therapeutic Implications

Ban

Siegfried

Apte

2018

Trends in Molecular Medicine

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Glaucoma is one of the leading causes of blindness globally, and is characterized by loss of retinal ganglion cells (RGCs). Because vision loss in glaucoma is not reversible, therapeutic interventions early in disease are highly desirable. However, owing to the current limitations in evaluating glaucomatous neurodegeneration, it is challenging to monitor the disease severity and progression objectively, and to design rational therapeutic strategies accordingly. Therefore, there is a clear need to identify quantifiable molecular biomarkers of glaucomatous neurodegeneration. As such, in our opinion, molecular biomarker(s) that specifically reflect stress or death of RGCs, and which correlate with disease severity, progression, and response to therapy, are highly desirable.

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GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

Cited by 37 publications

References 30 publications

Antithrombotic Therapy for Atrial Fibrillation

Antithrombotic Therapy for Atrial Fibrillation

HDAC5 promotes optic nerve regeneration by activating the mTOR pathway

Monitoring Neurodegeneration in Glaucoma: Therapeutic Implications

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