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Development of chemically induced choroidal injury models for the study and treatment of AMD
Han I, Pandala N, Haefeli L, Lang MJ, Stone EM, Mullins RF, Tucker BA (2024) Development of chemically induced choroidal injury models for the study and treatment of AMD. ARVO Annual Meeting 65(7):5382.
Objective: To describe the development of Age-Related Macular Degeneration (AMD) models through the targeted injury of choroidal cells in the eye.
Summary: Anti-CD38-SAP (BETA-016) and Anti-CD105-SAP (IT-80) were utilized to selectively lesion choroidal cells in the eyes of mice, creating an AMD model. Both agents demonstrated localized effects with no observed systemic toxicity at the administered doses, contrasting with the broader toxicity seen with Sodium Iodate, another lesioning agent examined.
Usage: Different doses of Anti-CD38-SAP and Anti-CD105-SAP (0.05, 0.25, and 0.5 mg/ml; 10 μL/eye) were injected suprachoroidally into the eyes of mice to induce the desired choroidal cell lesions.
Related Products: Anti-CD105-SAP (Cat. #IT-80)
Striatal parvalbumin interneurons are activated in a mouse model of cerebellar dystonia
Matsuda T, Morigaki R, Hayasawa H, Koyama H, Oda T, Miyake K, Takagi Y (2024) Striatal parvalbumin interneurons are activated in a mouse model of cerebellar dystonia. Dis Model Mech 17(5):dmm050338. doi: 10.1242/dmm.050338 PMID: 38616770
Objective: To examine the influence of cerebellar abnormalities on the basal ganglia circuitry to investigate dystonia pathophysiology.
Summary: Dystonia is a disorder characterized by twisting, repetitive movements, and abnormal postures induced by sustained muscle contractions. This study utilized a cerebellar dystonia mouse model to examine the cerebellum’s contribution. The authors found that modulating parvalbumin (PV) interneurons might provide a novel treatment strategy.
Usage: In order to selectively ablate dorsolateral striatal PV interneurons, Streptavidin-ZAP (Cat. #IT-27) was mixed equimolar with biotinylated anti-PV and diluted with PBS by 1:100 and 3 ul injected into the striatum of mice. BIgG-SAP Rabbit (Cat. #IT-75) was used as the control.
Related Products: Streptavidin-ZAP (Cat. #IT-27), BIgG-SAP Rabbit (Cat. #IT-75)
Brain areas interconnected to ventral pathway circuits are independently able to induce enhancement in object recognition memory and cause reversal in object recognition memory deficit
Masmudi-Martín M, Navarro-Lobato I, López-Aranda MF, Quiros-Ortega ME, Carretero-Rey M, Garcia-Garrido MF, López Téllez JF, Jiménez-Recuerda I, Muñoz de Leon López CA, Khan ZU (2024) Brain areas interconnected to ventral pathway circuits are independently able to induce enhancement in object recognition memory and cause reversal in object recognition memory deficit. CNS Neurosci Ther 30(4):e14727. doi: 10.1111/cns.14727 PMID: 38644593
Objective: Use OX7-SAP to create an object-recognition memory deficit model in rats.
Summary: Ventral pathway circuits are responsible for part of object recognition memory. Lesioning with OX7-SAP, a way to selectively remove CD90-expressing neuronal cells, can create a knockout model of object recognition memory, and lesioning in specific parts of the brain can construct a map of object recognition memory function.
Usage: Rats were lesioned with OX7-SAP in either the brain’s perirhinal cortex, frontal cortex, or Area V2 and assessed for object recognition memory deficits. (0.2μg in 1μL, IT-02)
Related Products: OX7-SAP (Cat. #IT-02)
Cetuximab-toxin conjugate and npe6 with light enhanced cytotoxic effects in head and neck squamous cell carcinoma in vitro
Komatsu N, Kosai A, Kuroda M, Hamakubo T, Abe T (2024) Cetuximab-toxin conjugate and npe6 with light enhanced cytotoxic effects in head and neck squamous cell carcinoma in vitro. Biomedicines 12(5):973. doi: 10.3390/biomedicines12050973 PMID: 38790935
Objective: Combine the use of antibody-directed saporin and a photosensitizer to exert directed and improved cytotoxicity towards carcinoma cells as compared to either by itself.
Summary: Photodynamic therapy uses photosensitizers and irradiation to exert cytotoxic effects on cancer. When combined with biotinylated anti-EGFR conjugated to Strep-ZAP (IT-27), an increased cytotoxicity was hypothesized. The method developed enhanced the cytotoxicity of anti-EGFR-Strep-ZAP by the photodynamic effect in Sa3 and HO-1-u-1 cells, which have moderate levels of EGFR expression.
Usage: Cells were seeded on a 96-well plate and delivered 1.34 pM to 4.2 nM of anti-EGFR or anti-EGFR-Strep-ZAP, and cell viability was measured with formazan.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861
Schulze FJ, Asadian-Birjand M, Pradela M, Niesler N, Nagal G, Fuchs H, (2024) A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861. BMC Biotechnol 24(1):24. doi: 10.1186/s12896-024-00854-5 PMID: 38685061
Objective: To examine whether the addition of the molecular adapter, that consists of a cell penetrating peptide and two cleavable peptides, further augments the endosomal escape enhancement of the glycosylated triterpenoid SO1861, which has shown up to more than 1000‑fold enhancement in the past.
Summary: Introducing the peptide adapter into the targeted toxin led to an about 12‑fold enhancement in the cytotoxicity on target cells while SO1861 caused a 430‑fold increase. However, the combination of adapter and glycosylated triterpenoid resulted in a more than 4300‑fold enhancement and in addition to a 51‑fold gain in specificity.
Usage: When inserting the adapter A2 between the ribosome-inactivating protein, saporin (PR-01) and the targeting moiety EGF (Saporin-A2-EGF), an improved anti-cancer effect in mice with EGFR-positive tumors and simultaneously lesser side effects were observed in comparison to Saporin-EGF.
Related Products: Saporin (Cat. #PR-01)
A pupillary contrast response in mice and humans: Neural mechanisms and visual functions
Fitzpatrick MJ, Krizan J, Hsiang JC, Shen N, Kerschensteiner D (2024) A pupillary contrast response in mice and humans: Neural mechanisms and visual functions. Neuron 112(14):2404-2422.e9. doi: 10.1016/j.neuron.2024.04.012 PMID: 38697114
Objective: To show that temporal contrast drives pupil constriction through a cell-type-specific retinal circuit in mice and humans.
Summary: The pupillary contrast response enhances high spatial frequency contrast in retinal images and improves visual acuity.
Usage: Immunohistochemistry (1:2000) (Cat: AB-N38).
Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)
A new Opn4cre recombinase mouse line to target intrinsically photosensitive retinal ganglion cells (ipRGCs)
Dyer B, Yu SO, Lane Brown R, Lang RA, D’Souza SP (2024) A new Opn4cre recombinase mouse line to target intrinsically photosensitive retinal ganglion cells (ipRGCs). bioRxiv 2024.04.16.589750. doi: 10.1101/2024.04.16.589750 PMID: 38659888
Objective: To generate a new Opn4cre knock-in allele [Opn4cre(DSO)], in which cre is placed immediately downstream of the Opn4 start codon.
Summary: The Opn4cre(DSO) mouse line improves the specificity of ipRGC labeling, enabling the targeted study of these cells in relation to light-regulated behaviors and physiology.
Usage: Histology and immunofluorescence.
Related Products: Melanopsin Rabbit Polyclonal, affinity-purified (Cat. #AB-N39)
Novel loading protocol combines highly efficient encapsulation of exogenous therapeutic toxin with preservation of extracellular vesicles properties, uptake and cargo activity
Zuppone S, Zarovni N, Noguchi K, Loria F, Morasso C, Lõhmus A, Nakase I, Vago R (2024) Novel loading protocol combines highly efficient encapsulation of exogenous therapeutic toxin with preservation of extracellular vesicles properties, uptake and cargo activity. Discov Nano 19(1):76. doi: 10.1186/s11671-024-04022-8 PMID: 38691254
Objective: Extracellular vesicles (EVs) have been investigated as carriers of biological therapeutics such as proteins and RNA as well as small-molecule drugs. The objective was to test a strategy of EV loading based on temporary pH alteration through incubation of EVs with alkaline sodium carbonate, which results in conspicuous exogenous molecule incorporation.
Summary: The encapsulated saporin resulted protected from degradation and was efficiently conveyed to receiving cancer cells and triggered cell death. EV-delivered saporin was more cytotoxic compared to the free toxin. This approach allows both the structural preservation of vesicle properties and the transfer of protected cargo in the context of drug delivery.
Usage: Authors used fluorescently labeled saporin, SAP-FITC, and a nano-sized EV-to-cargo ratio of 1:1.5 (w:w).
Related Products: Saporin Goat Polyclonal, affinity-purified FITC-labeled (Cat. #AB-15AP-FL)
Estradiol’s role in timely puberty onset in the ewe
Aerts EG (2024) Estradiol’s role in timely puberty onset in the ewe. Western Virginia Univ Thesis.
Objective: To investigate the role of arcuate nucleus KNDy (kisspeptin/neurokinin B/dynorphin) neurons in regulating the timing of puberty onset and estradiol (E2) sensitivity in female sheep.
Summary: Ablation of approximately 75% of KNDy neurons using NKB-SAP in the arcuate nucleus significantly delayed puberty onset and blunted the luteinizing hormone (LH) surge, demonstrating that KNDy neurons are critical for timely puberty in ewes. However, animals retained the ability to respond to NK3R agonist senktide, suggesting upstream populations may mediate estradiol negative feedback.
Usage: NKB-SAP (IT-63) was bilaterally injected into the arcuate nucleus (1 µg/side in 1 µL) to ablate NK3R-expressing KNDy neurons and evaluate their role in pubertal timing and LH regulation.
Related Products: NKB-SAP (Cat. #IT-63)
Involvement of the transient receptor channels in preclinical models of musculoskeletal pain
Kudsi SQ, Viero FT, Pereira LG, Trevisan G (2024) Involvement of the transient receptor channels in preclinical models of musculoskeletal pain. Curr Neuropharmacol 22(1):72-87. doi: 10.2174/1570159X21666230908094159 PMID: 37694792
Objective: To provide an updated view of the most studied preclinical models of muscle hyperalgesia and the role of transient receptor potential (TRP) in these models.
Summary: The participation of TRPV1, TRPA1, and TRPV4 in different models of musculoskeletal pain was evaluated using pharmacological and genetic tools. All the studies detected the antinociceptive effect of respective antagonists or reduced nociception in knockout mice. Hence, TRPV1, TRPV4, and TRPA1 blockers could potentially be utilized in the future for inducing analgesia in muscle hypersensitivity pathologies.
Usage: NK1-expressing neurons were ablated by SP-SAP (neurotoxin saporin conjugated to substance P) to Vc, and the ablation of NK1-expressing second-order neurons reduced the MGS and bite force nociceptive behaviors.
Related Products: SP-SAP (Cat. #IT-07)
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