Real-Time Imaging of Single Retinal Cell Apoptosis in a Non-Human Primate Ocular Hypertension Model.
Transl Vis Sci Technol
; 13(1): 20, 2024 01 02.
Article
en En
| MEDLINE
| ID: mdl-38252520
ABSTRACT
Purpose:
To evaluate the feasibility of using DARC (detection of apoptosing retinal cells) technology as a biomarker for preclinical assessment of glaucomatous damage in a non-human primate (NHP) model of ocular hypertension (OHT).Methods:
Elevated intraocular pressure (IOP) was induced by applying a laser to the trabecular meshwork in each eye of NHPs. Changes in DARC counts in the retina, identified as fluorescent-tagged annexin V (ANX776)-positive cells, were evaluated together with optic nerve damage, assessed using spectral domain-optical coherence tomography. The pharmacokinetic properties of ANX776 in both healthy and OHT model monkeys were also examined.Results:
Sustained elevation of IOP and subsequent thinning of the retinal nerve fiber layer thickness (RNFLT) around the optic nerve head were confirmed in the OHT model. Increases in DARC counts were also detected after IOP elevation. We identified a statistically significant relationship between cumulative DARC counts and reductions in RNFLT both globally and in each peripapillary sector. Intravenous administration of ANX776 increased blood annexin V in a dose-dependent manner, which was subsequently eliminated.Conclusions:
This study revealed that DARC technology can effectively assess glaucomatous damage in an NHP OHT model. We obtained the fundamental data that could serve as a reference for developing preclinical models to evaluate the pharmacodynamics of neuroprotective agents using DARC technology in NHP OHT models. Translational Relevance Our basic data in a monkey OHT model could be useful for future preclinical studies using DARC technology to estimate the pharmacodynamic response of neuroprotective agents.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_arterial_hypertension
/
6_cardiovascular_diseases
/
6_other_malignant_neoplasms
/
6_sense_organ_diseases
Asunto principal:
Glaucoma
/
Hipertensión Ocular
/
Fármacos Neuroprotectores
Límite:
Animals
Idioma:
En
Revista:
Transl Vis Sci Technol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón