Retinopathy of Prematurity

Bashinsky, Alice L

doi:10.18043/ncm.78.2.124

Cited by 83 publications

(106 citation statements)

References 11 publications

(12 reference statements)

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“…In addition, vitreoretinal neovascularization can promote traction retinal detachment, leading to blindness [5]. In the United States, 14,000–16,000 premature infants are affected by ROP annually [6,7]. Conventional therapeutic options include laser ablation and the anti-vascular endothelial growth factor (VEGF) therapy, which both have their limitations and complications.…”

Section: Introductionmentioning

confidence: 99%

Blockade of TREM-1 prevents vitreoretinal neovascularization in mice with oxygen-induced retinopathy

Rojas

Caldwell

Sigalov

2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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In pathological retinal neovascularization (RNV) disorders, the retina is infiltrated by activated leukocytes and macrophages. Triggering receptor expressed on myeloid cells 1 (TREM-1), an inflammation amplifier, activates monocytes and macrophages and plays an important role in cancer, autoimmune and other inflammation-associated disorders. Hypoxia-inducible TREM-1 is involved in cancer angiogenesis but its role in RNV remains unclear. Here, to close this gap, we evaluated the role of TREM-1 in RNV using a mouse model of oxygen-induced retinopathy (OIR). We found that hypoxia induced overexpression of TREM-1 in the OIR retinas compared to that of the room air group. TREM-1 was observed specifically in areas of pathological RNV, largely colocalizing with macrophage colony-stimulating factor (M-CSF) and CD45- and Iba-1-positive cells. TREM-1 blockade using systemically administered first-in-class ligand-independent TREM-1 inhibitory peptides rationally designed using the signaling chain homooligomerization (SCHOOL) strategy significantly (up to 95%) reduced vitreoretinal neovascularization. The peptides were well-tolerated when formulated into lipopeptide complexes for peptide half-life extension and targeted delivery. TREM-1 inhibition substantially downregulated retinal protein levels of TREM-1 and M-CSF suggesting that TREM-1-dependent suppression of pathological angiogenesis involves M-CSF. Targeting TREM-1 using TREM-1-specific SCHOOL peptide inhibitors represents a novel strategy to treat retinal diseases that are accompanied by neovascularization including retinopathy of prematurity.

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Section: Introductionmentioning

confidence: 99%

Blockade of TREM-1 prevents vitreoretinal neovascularization in mice with oxygen-induced retinopathy

Rojas

Caldwell

Sigalov

2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…In addition, vitreoretinal neovascularization can promote traction retinal detachment, leading to blindness (Al-Shabrawey et al, 2013). In the United States, 14,000-16,000 premature infants are affected by ROP annually and about 4.1 million adults over 40 years have DR (Bashinsky, 2017;Hartnett, 2017). Complications of conventional therapeutic options including laser ablation (corneal edema, anterior chamber reaction, intraocular hemorrhage, cataract formation, and intraocular pressure changes) (Mutlu & Sarici, 2013) and anti-VEGF therapy (damage of healthy vessels, potential side effects on neurons, rapid vascular regrowth upon interrupting the VEGF blockade, and limited effectiveness in some patients) (Maharaj et al, 2008;Mancuso et al, 2006;Pieramici & Rabena, 2008;Verheul & Pinedo, 2007) highlight an unmet need for new targeted therapies that can better address the pathogenesis of neovascular retinal diseases and improve their treatment.…”

Section: Retinopathymentioning

confidence: 99%

Targeting Intramembrane Protein–Protein Interactions: Novel Therapeutic Strategy of Millions Years Old

Sigalov

2018

Advances in Protein Chemistry and Structural Biology

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Intramembrane protein-protein interactions (PPIs) are involved in transmembrane signal transduction mediated by cell surface receptors and play an important role in health and disease. Recently, receptor-specific modulatory peptides rationally designed using a general platform of transmembrane signaling, the signaling chain homooligomerization (SCHOOL) model, have been proposed to therapeutically target these interactions in a variety of serious diseases with unmet needs including cancer, sepsis, arthritis, retinopathy, and thrombosis. These peptide drug candidates use ligand-independent mechanisms of action (SCHOOL mechanisms) and demonstrate potent efficacy in vitro and in vivo. Recent studies surprisingly revealed that in order to modify and/or escape the host immune response, human viruses use similar mechanisms and modulate cell surface receptors by targeting intramembrane PPIs in a ligand-independent manner. Here, I review these intriguing mechanistic similarities and discuss how the viral strategies optimized over a billion years of the coevolution of viruses and their hosts can help to revolutionize drug discovery science and develop new, disruptive therapies. Examples are given.

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“…Bashinsky provides information related to screening for retinopathy-impairment or loss of vision-of prematurity (ROP) [2], a leading cause of childhood blindness in premature infants. Screening for ROP is recommended for all infants with a birth weight of less than 1,500g or a gestational age of 30 weeks or less.…”

Section: Screening and Early Interventionmentioning

confidence: 99%

Introduction to The NCMJ's Special Issue on Vision and Hearing Loss

Williams

2017

North Carolina Medical Journal

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Retinopathy of Prematurity

Cited by 83 publications

References 11 publications

Blockade of TREM-1 prevents vitreoretinal neovascularization in mice with oxygen-induced retinopathy

Blockade of TREM-1 prevents vitreoretinal neovascularization in mice with oxygen-induced retinopathy

Targeting Intramembrane Protein–Protein Interactions: Novel Therapeutic Strategy of Millions Years Old

Introduction to The NCMJ's Special Issue on Vision and Hearing Loss

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