Erratum to “Ultrasound-mediated nanoparticle delivery across ex vivo bovine retina after intravitreal injection” [Eur. J. Pharm. Biopharm. 119 (2017) 125–136]

Fibrinogen plays a pathologic role in multiple diseases. It contributes to thrombosis and modifies inflammatory and immune responses, supported by studies in mice expressing fibrinogen variants with altered function or with a germline fibrinogen deficiency. However, therapeutic strategies to safely and effectively tailor plasma fibrinogen concentration are lacking. Here, we developed a strategy to tune fibrinogen expression by administering lipid nanoparticle (LNP)-encapsulated siRNA targeting the fibrinogen α chain (siFga). Three distinct LNP-siFga reagents reduced both hepatic Fga mRNA and fibrinogen levels in platelets and plasma, with plasma levels decreased to 42%, 16% and 4% of normal within one-week of administration. Using the most potent siFga, circulating fibrinogen was controllably decreased to 32%, 14%, and 5% of baseline with a 0.5, 1, and 2 mg/kg dose, respectively. Whole blood from mice treated with siFga formed clots with significantly decreased clot strength ex vivo, but siFga treatment did not compromise hemostasis following saphenous vein puncture or tail transection. In an endotoxemia model, siFga suppressed the acute phase response and decreased plasma fibrinogen, D-dimer, and proinflammatory cytokine levels. In a sterile peritonitis model, siFga restored normal macrophage migration in plasminogen-deficient mice. Finally, treatment of mice with siFga decreased the metastatic potential of tumour cells in a manner comparable to that observed in fibrinogen-deficient mice. The results indicate that siFga causes robust and controllable depletion of fibrinogen and provide the proof-of-concept that this strategy can modulate the pleiotropic effects of fibrinogen in relevant disease models.

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Melanopsin+RGCs Are fully Resistant to NMDA-Induced Excitotoxicity

International Journal of Molecular Sciences ◽

10.3390/ijms20123012 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3012 ◽

Cited By ~ 5

Author(s):

Beatriz Vidal-Villegas ◽

Johnny Di Pierdomenico ◽

Juan A Miralles de Imperial-Ollero ◽

Arturo Ortín-Martínez ◽

Francisco M Nadal-Nicolás ◽

...

Keyword(s):

Intravitreal Injection ◽

Ganglion Cells ◽

Ex Vivo ◽

Retinal Ganglion ◽

Long Term Effects ◽

Pou Domain ◽

Short And Long Term ◽

Sd Oct

We studied short- and long-term effects of intravitreal injection of N-methyl-d-aspartate (NMDA) on melanopsin-containing (m+) and non-melanopsin-containing (Brn3a+) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using Spectral Domain-Optical Coherence Tomography (SD-OCT). Ex vivo analyses were done at 3, 7, or 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for brain-specific homeobox/POU domain protein 3A (Brn3a) and melanopsin (m), the total number of Brn3a+RGCs and m+RGCs were quantified, and their topography represented. In control retinas, the mean total numbers of Brn3a+RGCs and m+RGCs were 78,903 ± 3572 and 2358 ± 144 (mean ± SD; n = 10), respectively. In the NMDA injected retinas, Brn3a+RGCs numbers diminished to 49%, 28%, 24%, and 19%, at 3, 7, 14 days, and 15 months, respectively. There was no further loss between 7 days and 15 months. The number of immunoidentified m+RGCs decreased significantly at 3 days, recovered between 3 and 7 days, and were back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induced within a week a rapid loss of 72% of Brn3a+RGCs, a transient downregulation of melanopsin expression (but not m+RGC death), and a thinning of the inner retinal layers.

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Elongate microparticles for enhanced peptide and nanoparticle delivery to ex vivo pig skin

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2015.02.842 ◽

2015 ◽

Vol 72 (5) ◽

pp. AB208

Keyword(s):

Ex Vivo ◽

Nanoparticle Delivery ◽

Pig Skin

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Effect of hydrogen peroxide on amino acid concentrations in bovine retina and vitreous humor, ex vivo

Methods and Findings in Experimental and Clinical Pharmacology ◽

10.1358/mf.2003.25.9.793336 ◽

2003 ◽

Vol 25 (9) ◽

pp. 695 ◽

Cited By ~ 3

Author(s):

A.M. LeDay ◽

S. Ganguly ◽

K.H. Kulkarni ◽

A. Dash ◽

C.A. Opere ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Amino Acid ◽

Ex Vivo ◽

Vitreous Humor ◽

Bovine Retina ◽

Amino Acid Concentrations

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Nanotechnology in Neurology—Current Status and Future Possibilities

US Neurology ◽

10.17925/usn.2010.06.01.12 ◽

2010 ◽

Vol 06 (01) ◽

pp. 12 ◽

Cited By ~ 4

Author(s):

James M Provenzale ◽

Aaron M Mohs ◽

◽

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Ex Vivo ◽

Current Status ◽

Medical Applications ◽

Nanoparticle Delivery ◽

New Methods ◽

The Central Nervous System ◽

Neuro Protection

The field of nanomedicine is rapidly emerging and will provide many novel methods for diagnosis and treatment. In this article the applications of nanotechnology to the central nervous system (CNS) will be described. Nanotechnology provides many potential solutions to various problems encountered in CNS diseases. Specifically, nanomedicine offers the possibility of new methods of drug delivery, more sensitive and specific means for diagnosis of disease at earlier stages and assessment of treatment response, and also potential techniques for neuro-protection and neuro-engineering. In this article, information is provided on the various types of nanoparticles involved in medical applications, the principles of nanoparticle delivery and targeting, and bothin vivoandex vivouses of nanoscale materials.

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Morphological actions of isoprostanes on bovine retina, ex vivo

The FASEB Journal ◽

10.1096/fasebj.22.1_supplement.1137.7 ◽

2008 ◽

Vol 22 (S1) ◽

Author(s):

Min Zhao ◽

Guilin Zhan ◽

Yan Zhang ◽

Sunny E Ohia ◽

Catherine A Opere

Keyword(s):

Ex Vivo ◽

Bovine Retina

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Targeted Nanoparticle Delivery of Doxorubicin Into Placental Tissues to Treat Ectopic Pregnancies

Endocrinology ◽

10.1210/en.2012-1832 ◽

2013 ◽

Vol 154 (2) ◽

pp. 911-919 ◽

Cited By ~ 25

Author(s):

Tu’uhevaha J. Kaitu’u-Lino ◽

Scott Pattison ◽

Louie Ye ◽

Laura Tuohey ◽

Pavel Sluka ◽

...

Keyword(s):

Ectopic Pregnancy ◽

Ex Vivo ◽

Growth Factor Receptor ◽

Nanoparticle Delivery ◽

Dependent Inhibition ◽

Life Threatening ◽

Choriocarcinoma Cells ◽

Ectopic Pregnancies

Abnormal trophoblast growth can cause life-threatening disorders such as ectopic pregnancy, choriocarcinoma, and placenta accreta. EnGeneIC Delivery Vehicles (EDVs) are nanocells that can promote tissue-specific delivery of drugs and may be useful to medically treat such disorders. The objective of this study was to determine whether EDVs loaded with the chemotherapeutic doxorubicin and targeting the epidermal growth factor receptor (EGFR, very highly expressed on the placental surface) can regress placental cells in vitro, ex vivo, and in vivo. In female SCID mice, EGFR-targeted EDVs induced greater inhibition of JEG-3 (choriocarcinoma cells) tumor xenografts, compared with EDVs targeting an irrelevant antigen (nontargeted EDVs) or naked doxorubicin. EGFR-targeted EDVs were more readily taken up by human placental explants ex vivo and induced increased apoptosis (M30 antibody) compared with nontargeted EDVs. In vitro, EGFR-targeted EDVs administered to JEG-3 cells resulted in a dose-dependent inhibition of cell viability, proliferation, and increased apoptosis, a finding confirmed by continuous monitoring by xCELLigence. In conclusion, EGFR-targeted EDVs loaded with doxorubicin significantly inhibited trophoblastic tumor cell growth in vivo and in vitro and induced significant cell death ex vivo, potentially mediated by increasing apoptosis and decreasing proliferation. EDVs may be a novel nanoparticle treatment for ectopic pregnancy and other disorders of trophoblast growth.

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Melanopsin+RGCs Are Fully Resistant to NMDA-Induced Excitotoxicity

10.20944/preprints201905.0278.v1 ◽

2019 ◽

Author(s):

Beatriz Vidal-Villegas ◽

Johnny Di Pierdomenico ◽

Juan Antonio Miralles de Imperial-Ollero ◽

Arturo Ortín-Martínez ◽

Francisco Manuel Nadal-Nicolás ◽

...

Keyword(s):

Intravitreal Injection ◽

Ganglion Cells ◽

Ex Vivo ◽

Retinal Ganglion ◽

Long Term Effects ◽

Short And Long Term ◽

The Mean ◽

Sd Oct

We studied short- and long-term effects of intravitreal injection of N-methyl-D-aspartate (NMDA) on melanopsin-containing (m+) and non-melanopsin-containing (Brn3a+) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received  a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using SD-OCT.  Ex vivo analyses were done at 3, 7, 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for Brn3a and melanopsin, the total number of Brn3a+RGCs and m+RGCs were quantified and their topography represented. In control retinas, the mean total numbers of Brn3a+RGCs and m+RGCs were 78,903±3,572 and 2,358±144 (mean ± SD; n=10), respectively. In the NMDA injected retinas, Brn3a+RGCs numbers diminished to 50% and 25%, at 3 and 14 days, respectively, but there was no further loss up to 15 months. The number of immunoidentified m+RGCs decreased significantly at 3 days, recovered between 3-7 days and was back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induce a rapid loss of 75% of Brn3a+RGCs, a transient downregulation of melanopsin expression but not m+RGC death, and a thinning of the inner retinal layers.

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