ArticleMolecular vision2012
Electroporation-mediated gene delivery of cleavage-resistant pro-nerve growth factor causes retinal neuro- and vascular degeneration.
Article in Molecular vision, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- The innate immune system in diabetic retinopathy.Progress in retinal and eye research · 2021Review
- Modulating Expression of Thioredoxin Interacting Protein (TXNIP) Prevents Secondary Damage and Preserves Visual Function in a Mouse Model of Ischemia/Reperfusion.International journal of molecular sciences · 2019Article
- Palmitic Acid Induces Müller Cell Inflammation that is Potentiated by Co-treatment with Glucose.Scientific reports · 2018Article
- Inducible overexpression of endothelial proNGF as a mouse model to study microvascular dysfunction.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- Deletion of the Neurotrophin Receptor p75Journal of diabetes, metabolic disorders & control · 2017Article
- Implication of the neurotrophin receptor p75Expert review of ophthalmology · 2017Article
- Imbalance of the Nerve Growth Factor and Its Precursor: Implication in Diabetic Retinopathy.Journal of clinical & experimental ophthalmology · 2015Article
- Gene therapy to treat inherited and complex retinal degenerative diseases.Molecular therapy. Methods & clinical development · 2015Article
- Silencing p75(NTR) prevents proNGF-induced endothelial cell death and development of acellular capillaries in rat retina.Molecular therapy. Methods & clinical development · 2015Article
- Nerve growth factor in diabetic retinopathy: beyond neurons.Expert review of ophthalmology · 2014Article
- Deletion of thioredoxin-interacting protein preserves retinal neuronal function by preventing inflammation and vascular injury.British journal of pharmacology · 2014Article
- Involvement of NT3 and P75(NTR) in photoreceptor degeneration following selective Müller cell ablation.Journal of neuroinflammation · 2013Article
- Modulation of p75(NTR) prevents diabetes- and proNGF-induced retinal inflammation and blood-retina barrier breakdown in mice and rats.Diabetologia · 2013Article
- Diabetes and overexpression of proNGF cause retinal neurodegeneration via activation of RhoA pathway.PloS one · 2013Article
- Pronerve growth factor induces angiogenesis via activation of TrkA: possible role in proliferative diabetic retinopathy.Journal of diabetes research · 2013Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeNeurotrophins, including nerve growth factor (NGF), are secreted by glia as a pro-form (proNGF) that is normally cleaved into the mature ligand. Increases of proNGF has been well documented in retinal neurodegenerative diseases. Since systemic overexpression of proNGF exhibits embryonic lethality, we aimed to establish a model that specifically and stably overexpresses a cleavage-resistant mutant of proNGF (proNGF123) plasmid in the retina using electroporation.
methodsMale Sprague-Dawley rats were injected intravitreally with pGFP or pGFP-proNGF123 plasmids, then electroporated with various settings for optimization. Retinal cell death and ganglion cell count were assessed by TUNEL and immunostaining with anti-Brn3. Expression of proNGF, NGF, and their receptors was examined by western blot. Retinal vascular permeability was assessed by extravasation of bovine serum albumin-fluorescein. Development of acellular capillaries was assessed by periodic acid-Schiff and hematoxylin staining.
resultsSuccessful pGFP-proNGF123 gene delivery and expression of proNGF was demonstrated by western blot and extensive proNGF immunostaining in retina sections. Overexpression of proNGF reduced NGF expression while inducing the expression of neurotrophin receptors, including p75(NTR) and tyrosine receptor kinase A, but not sortilin. Overexpression of proNGF resulted in ~50% reduction in ganglion cell count and fivefold increase in TUNEL-positive cells in rat retina. In addition, overexpression of proNGF induced breakdown of the blood-retina barrier evident by twofold increase in extravasation of bovine serum albumin-fluorescein after 1 week and induced the development of acellular capillaries after 4 weeks.
conclusionsElectroporation can successfully incorporate and express biologically active cleavage-resistant proNGF locally in rat retinas. Overexpression of cleavage-resistant proNGF can be a useful tool to investigate specific molecular mechanisms by which proNGF causes neurodegeneration and vascular injury in the retina.
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Identifiers
23288991PMC3534146W1500979680What OpenQuestion holds
Registered trials
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