Microsphere antioxidant and sustained erythropoietin-R76E release functions cooperate to reduce traumatic optic neuropathy

DeJulius, Carlisle; Bernardo-Colón, Alexandra; Naguib, Sarah; Backstrom, Jon R.; Kavanaugh, Taylor E.; Gupta, Mukesh Kumar; Duvall, Craig L.; Rex, Tonia S.

doi:10.1016/j.jconrel.2020.10.010

Cited by 19 publications

(44 citation statements)

References 42 publications

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“…TON in human can be recapitulated in mice models [ 124 , 179 , 180 , 181 ]. There are two major TON animal models used in previous studies, namely, optic nerve crush (ONC) and ocular blast injury.…”

Section: Experimental Models Of Retinal Ganglion Cell Degeneration To Study Oxidative Stressmentioning

confidence: 99%

Role of Oxidative Stress in Ocular Diseases Associated with Retinal Ganglion Cells Degeneration

Kang

Liu

Wen³

et al. 2021

Antioxidants

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Ocular diseases associated with retinal ganglion cell (RGC) degeneration is the most common neurodegenerative disorder that causes irreversible blindness worldwide. It is characterized by visual field defects and progressive optic nerve atrophy. The underlying pathophysiology and mechanisms of RGC degeneration in several ocular diseases remain largely unknown. RGCs are a population of central nervous system neurons, with their soma located in the retina and long axons that extend through the optic nerve to form distal terminals and connections in the brain. Because of this unique cytoarchitecture and highly compartmentalized energy demand, RGCs are highly mitochondrial-dependent for adenosine triphosphate (ATP) production. Recently, oxidative stress and mitochondrial dysfunction have been found to be the principal mechanisms in RGC degeneration as well as in other neurodegenerative disorders. Here, we review the role of oxidative stress in several ocular diseases associated with RGC degenerations, including glaucoma, hereditary optic atrophy, inflammatory optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and drug toxicity. We also review experimental approaches using cell and animal models for research on the underlying mechanisms of RGC degeneration. Lastly, we discuss the application of antioxidants as a potential future therapy for the ocular diseases associated with RGC degenerations.

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Section: Experimental Models Of Retinal Ganglion Cell Degeneration To Study Oxidative Stressmentioning

confidence: 99%

Role of Oxidative Stress in Ocular Diseases Associated with Retinal Ganglion Cells Degeneration

Kang

Liu

Wen³

et al. 2021

Antioxidants

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“…have harnessed PPS‐based microspheres loaded with erythropoietin‐R76E (EPO‐R67E) as a model drug for ameliorating traumatic optic neuropathy. [ 165 ] The ROS‐degradable and PPS‐ scavenging NPs showed a sustained release profile. In the animal model, drug‐loaded PPS microspheres alleviated the symptoms of disease, including high inflammation levels, neuron degeneration, and decreased visual function.…”

Section: Polymer‐based Delivery Of Antioxidantsmentioning

confidence: 99%

Polymeric Antioxidant Materials for Treatment of Inflammatory Disorders

Yeo

Lee

et al. 2021

Advanced Therapeutics

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Reactive oxygen and nitrogen species (RONS) play a key role in physiological conditions as signaling molecules for regulating homeostasis in the human body. However, abnormally increased RONS levels can damage DNA, protein, and tissue, or even impair cellular signaling. Consequently, when this state is present for a long time, it can lead to severe inflammatory disorders, such as lupus, diabetes, rheumatoid arthritis, Crohn's disease, and neurodegenerative disorders. Although antioxidant therapies have been developed for a long time to treat acute or chronic inflammatory diseases, small molecule‐based antioxidants showed relatively low therapeutic effects due to rapid clearance and low stability in the bloodstream. As one of the solutions to overcome such limitations, incorporating polymers would provide enhanced blood stability, bioavailability, and even enhanced therapeutic effects. Herein, diverse polymeric antioxidant materials are introduced that are categorized into simple loading strategies and polymers with inherent antioxidative activity. Further, preclinical and clinical studies of polymeric antioxidant materials for anti‐inflammatory therapy are discussed and a better direction is provided for these to be pursued and improved in anti‐inflammatory therapy.

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“…Encapsulation of proteins with nano-formulation shows efficient delivery of retinoprotective proteins. For example, the intravitreal delivery of the neuroprotective peptide erythropoietin (EPO) is improved with the use of microparticles formulated with EPO and the hydrolytically degradable poly(lactic-co-glycolic acid) (PLGA) or the reactive oxygen species (ROS)-degradable poly(propylene sulfide) (PPS) in models of blast injury-induced retinal damage [66]. This research warrants the use of encapsulating PEDF in similar microparticles system to control and extend its release locally using in vivo retinopathy mouse models.…”

Section: Future Directions For Protein Delivery Systems In Ocular Researchmentioning

confidence: 99%

Delivery Systems of Retinoprotective Proteins in the Retina

Rebustini¹,

Bernardo-Colón²,

Nalvarte³

et al. 2021

IJMS

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Retinoprotective proteins play important roles for retinal tissue integrity. They can directly affect the function and the survival of photoreceptors, and/or indirectly target the retinal pigment epithelium (RPE) and endothelial cells that support these tissues. Retinoprotective proteins are used in basic, translational and in clinical studies to prevent and treat human retinal degenerative disorders. In this review, we provide an overview of proteins that protect the retina and focus on pigment epithelium-derived factor (PEDF), and its effects on photoreceptors, RPE cells, and endothelial cells. We also discuss delivery systems such as pharmacologic and genetic administration of proteins to achieve photoreceptor survival and retinal tissue integrity.

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Microsphere antioxidant and sustained erythropoietin-R76E release functions cooperate to reduce traumatic optic neuropathy

Cited by 19 publications

References 42 publications

Role of Oxidative Stress in Ocular Diseases Associated with Retinal Ganglion Cells Degeneration

Role of Oxidative Stress in Ocular Diseases Associated with Retinal Ganglion Cells Degeneration

Polymeric Antioxidant Materials for Treatment of Inflammatory Disorders

Delivery Systems of Retinoprotective Proteins in the Retina

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