ArticleExperimental neurology2022
Preclinical investigation of Pegylated arginase 1 as a treatment for retina and brain injury.
Article in Experimental neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 41 citations in OpenAlex.
- Novel Role of AcylCoA: Cholesterol Acyltransferase 1/Sterol O-Acyltransferase 1 (ACAT1/SOAT1) in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Article
- Myeloid HDAC3 deletion protects against traumatic optic injury.Cell death discovery · 2026Article
- Inhibition of pathological angiogenesis in oxygen-induced retinopathy by arginine depletion with ADI-PEG20.Experimental eye research · 2026Article
- S-ketamine exposure in early postnatal period induces social deficit mediated by excessive microglial synaptic pruning.Molecular psychiatry · 2025Article
- Deletion of myeloid HDAC3 promotes efferocytosis to ameliorate retinal ischemic injury.Journal of neuroinflammation · 2024Article
- Calbindin 2-specific deletion of arginase 2 preserves visual function after optic nerve crush.Cell death & disease · 2023Article
- The arginase 1/ornithine decarboxylase pathway suppresses HDAC3 to ameliorate the myeloid cell inflammatory response: implications for retinal ischemic injury.Cell death & disease · 2023Article
- Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Role of acyl-coenzyme A: cholesterol transferase 1 (ACAT1) in retinal neovascularization.Journal of neuroinflammation · 2023Article
- Systemic Administration of Pegylated Arginase-1 Attenuates the Progression of Diabetic Retinopathy.Cells · 2022Article
- Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic repair.Cell death & disease · 2022Article
- Novel Therapeutics for Diabetic Retinopathy and Diabetic Macular Edema: A Pathophysiologic Perspective.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Arginase 1 (A1) is the enzyme that hydrolyzes the amino acid, L-arginine, to ornithine and urea. We have previously shown that A1 deletion worsens retinal ischemic injury, suggesting a protective role of A1. In this translational study, we aimed to study the utility of systemic pegylated A1 (PEG-A1, recombinant human arginase linked to polyethylene glycol) treatment in mouse models of acute retinal and brain injury. Cohorts of WT mice were subjected to retinal ischemia-reperfusion (IR) injury, traumatic optic neuropathy (TON) or brain cerebral ischemia via middle cerebral artery occlusion (MCAO) and treated with intraperitoneal injections of PEG-A1 or vehicle (PEG only). Drug penetration into retina and brain tissues was measured by western blotting and immunolabeling for PEG. Neuroprotection was measured in a blinded fashion by quantitation of NeuN (neuronal marker) immunolabeling of retina flat-mounts and brain infarct area using triphenyl tetrazolium chloride (TTC) staining. Furthermore, ex vivo retina explants and in vitro retina neuron cultures were subjected to oxygen-glucose deprivation (OGD) followed by reoxygenation (R) and treated with PEG-A1. PEG-A1 given systemically did not cross the intact blood-retina/brain barriers in sham controls but reached the retina and brain after injury. PEG-A1 provided neuroprotection after retinal IR injury, TON and cerebral ischemia. PEG-A1 treatment was also neuroprotective in retina explants subjected to OGD/R but did not improve survival in retinal neuronal cultures exposed to OGD/R. In summary, systemic PEG-A1 administration is neuroprotective and provides an excellent route to deliver the drug to the retina and the brain after acute injury.
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