Role of Histamine H3 Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma

Autor: Silvia Sgambellone, Katarzyna Kieć-Kononowicz, Alessandro Pini, Stefano Catarinicchia, Mariaconcetta Durante, Dorota Łażewska, Cecilia Lanzi, Emanuela Masini, Laura Lucarini, Holger Stark
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
medicine.medical_specialty
Intraocular pressure
genetic structures
Ocular hypertension
Timolol
Imetit
Catalysis
intraocular pressure (IOP)
Inorganic Chemistry
lcsh:Chemistry
03 medical and health sciences
Histamine receptor
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Ciproxifan
medicine
oxidative stress
Physical and Theoretical Chemistry
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
business.industry
Organic Chemistry
baroprotection
H3R antagonists
General Medicine
Baroprotection
Glaucoma
H
3
R antagonists
Histamine
Intraocular pressure (IOP)
Oxidative stress
Animals
Choroid
Disease Models
Animal
Histamine H3 Antagonists
Imidazoles
Mast Cells
Models
Biological
Ocular Hypertension
Oxidative Stress
RNA
Messenger
Rabbits
Receptors
Histamine H3
Retinal Ganglion Cells
Time Factors
Intraocular Pressure
medicine.disease
histamine
eye diseases
Computer Science Applications
Hypertonic saline
030104 developmental biology
Endocrinology
glaucoma
chemistry
lcsh:Biology (General)
lcsh:QD1-999
030221 ophthalmology & optometry
sense organs
Histamine H3 receptor
business
medicine.drug
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 4, p 981 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 4
ISSN: 1422-0067
Popis: Intraocular pressure (IOP) has a tendency to fluctuate throughout the day, reaching its peak in the early morning in healthy subjects or glaucoma patients. Likewise, histamine tone also fluctuates over time, being lower at nighttime. Numerous studies have demonstrated a correlation between short-term IOP fluctuation and glaucoma progression
however, it has not yet been determined whether histamine plays a role in IOP fluctuations. The aim of this research was to establish the distribution of the histamine receptor proteins and respective mRNAs in the eye by western blot, immunohistochemistry and RT-PCR in New Zealand rabbits. Furthermore, we used a transient ocular hypertension (OHT) model induced by injection of 50 µ
L of 5% hypertonic saline into the vitreous and a stable OHT model (100 µ
L 0.1% carbomer in the anterior chamber) to address the potential IOP-lowering ability of H3 receptor (H3R) antagonists (ciproxifan, DL76 and GSK189254). IOPs were performed with a Tono-Pen at baseline and 60, 120 and 240 min post treatment after transient OHT induction and, every day for 12 days in the stable OHT model. All histamine receptor subtypes were localized in the rabbit retina and ciliary body/trabecular meshwork. All the treatments lowered IOP in a dose-dependent fashion between 0.3% and 1%. More specifically, the effects were maximal with ciproxifan at 60 min post-dose (IOP60 change = &minus
18.84 ±
4.85 mmHg, at 1%), remained stable until 120 min (IOP120 change = &minus
16.38 ±
3.8 mmHg, at 1%) and decayed thereafter to reach baseline values at 240 min. These effects were highly specific and dependent on histamine release as pre-treatment with imetit (H3R agonist, 1%) or pyrilamine (H1R antagonist, 1%) largely blocked ciproxifan-mediated effects. Color Doppler ultrasound examination was performed to evaluate changes in ophtalmic artery resistivity index (RI) before and after repeated dosing with DL 76, GSK189254, ciproxifan and timolol. Chronic treatments with H3R antagonists and timolol improved the vascular performance of ophthalmic arteries and reduced retinal ganglion cell death. Oxidative stress was also reduced and measured 8-Hydroxy-2&prime
deoxyguanosine (8OHdG) expression, and by dihidroethydium (DHE) staining. These results demonstrated that the histamine system participates in IOP regulation and that H3R antagonists could represent a future promising therapy for glaucoma. Further studies should be focused on the long-term IOP circadian fluctuations.
Databáze: OpenAIRE
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