ArticlePloS one2013
Diabetes and overexpression of proNGF cause retinal neurodegeneration via activation of RhoA pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Dyslipidemia and reduced retinal layer thicknesses in mild to moderate non-proliferative diabetic retinopathy.American journal of translational research · 2024Article
- EYE-503: A Novel Retinoic Acid Drug for Treating Retinal Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Nerve Growth Factor Role on Retinal Ganglion Cell Survival and Axon Regrowth: Effects of Ocular Administration in Experimental Model of Optic Nerve Injury.Molecular neurobiology · 2019Article
- RhoA activation in axotomy-induced neuronal death.Experimental neurology · 2018Article
- Inducible overexpression of endothelial proNGF as a mouse model to study microvascular dysfunction.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- Fasudil, a Clinically Used ROCK Inhibitor, Stabilizes Rod Photoreceptor Synapses after Retinal Detachment.Translational vision science & technology · 2017Article
- Deletion of the Neurotrophin Receptor p75Journal of diabetes, metabolic disorders & control · 2017Article
- Retraction: Diabetes and Overexpression of proNGF Cause Retinal Neurodegeneration via Activation of RhoA Pathway.PloS one · 2017Article
- Ginsenoside Rg1 Protects against Oxidative Stress-induced Neuronal Apoptosis through Myosin IIA-actin Related Cytoskeletal Reorganization.International journal of biological sciences · 2016Article
- Imbalance of the Nerve Growth Factor and Its Precursor: Implication in Diabetic Retinopathy.Journal of clinical & experimental ophthalmology · 2015Article
- Silencing p75(NTR) prevents proNGF-induced endothelial cell death and development of acellular capillaries in rat retina.Molecular therapy. Methods & clinical development · 2015Article
- Gene therapy to treat inherited and complex retinal degenerative diseases.Molecular therapy. Methods & clinical development · 2015Article
- Tiam1-Rac1 Axis Promotes Activation of p38 MAP Kinase in the Development of Diabetic Retinopathy: Evidence for a Requisite Role for Protein Palmitoylation.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2015Article
- Imbalance of the nerve growth factor and its precursor as a potential biomarker for diabetic retinopathy.BioMed research international · 2015Article
- Nerve growth factor in diabetic retinopathy: beyond neurons.Expert review of ophthalmology · 2014Article
- Involvement of NT3 and P75(NTR) in photoreceptor degeneration following selective Müller cell ablation.Journal of neuroinflammation · 2013Article
- Pronerve growth factor induces angiogenesis via activation of TrkA: possible role in proliferative diabetic retinopathy.Journal of diabetes research · 2013Article
- Molecular mechanisms of diabetic retinopathy: potential therapeutic targets.Middle East African journal of ophthalmologyReview
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Corrections and comments
- Correction · 2014-04-29Duplication of/in Image · Investigation by Journal/Publisher ·
- Retraction · 2017-10-16Duplication of/in Image · Investigation by Company/Institution · Investigation by Journal/Publisher · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author ·
- Retracted
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Our previous studies showed positive correlation between accumulation of proNGF, activation of RhoA and neuronal death in diabetic models. Here, we examined the neuroprotective effects of selective inhibition of RhoA kinase in the diabetic rat retina and in a model that stably overexpressed the cleavage-resistance proNGF plasmid in the retina. Male Sprague-Dawley rats were rendered diabetic using streptozotocin or stably express cleavage-resistant proNGF plasmid. The neuroprotective effects of the intravitreal injection of RhoA kinase inhibitor Y27632 were examined in vivo. Effects of proNGF were examined in freshly isolated primary retinal ganglion cell (RGC) cultures and RGC-5 cell line. Retinal neurodegeneration was assessed by counting TUNEL-positive and Brn-3a positive retinal ganglion cells. Expression of proNGF, p75(NTR), cleaved-PARP, caspase-3 and p38MAPK/JNK were examined by Western-blot. Activation of RhoA was assessed by pull-down assay and G-LISA. Diabetes and overexpression of proNGF resulted in retinal neurodegeneration as indicated by 9- and 6-fold increase in TUNEL-positive cells, respectively. In vitro, proNGF induced 5-fold cell death in RGC-5 cell line, and it induced >10-fold cell death in primary RGC cultures. These effects were associated with significant upregulation of p75(NTR) and activation of RhoA. While proNGF induced TNF-α expression in vivo, it selectively activated RhoA in primary RGC cultures and RGC-5 cell line. Inhibiting RhoA kinase with Y27632 significantly reduced diabetes- and proNGF-induced activation of proapoptotic p38MAPK/JNK, expression of cleaved-PARP and caspase-3 and prevented retinal neurodegeneration in vivo and in vitro. Taken together, these results provide compelling evidence for a causal role of proNGF in diabetes-induced retinal neurodegeneration through enhancing p75(NTR) expression and direct activation of RhoA and p38MAPK/JNK apoptotic pathways.
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