Intravitreal Administration of Avacincaptad Pegol in a Nonhuman Primate Model of Dry Age‐Related Macular Degeneration DOI Creative Commons

Rintaro Fujii,

Mayumi Matsushita,

Yoshitaka Itani

et al.

Pharmacology Research & Perspectives, Journal Year: 2024, Volume and Issue: 13(1)

Published: Dec. 26, 2024

ABSTRACT The lack of effective treatments for dry age‐related macular degeneration (AMD) is in part due to a preclinical animal model that recapitulates features the clinical state including retinal pigment epithelium (RPE) degeneration, also known as geographic atrophy (GA). A nonhuman primate GA was developed and its responsiveness an approved treatment, avacincaptad pegol (ACP), complement C5 inhibitor, evaluated. Intravitreal (ivt) administration sodium iodate (SI) into one eye male Macaca fascicularis leads areas (mm 2 ) hyper‐ or hypo‐autofluorescence. Qualitative changes structure over time were observed with spectral domain optical coherence tomography (OCT). Six days after SI administration, prior mean (± SEM) all eyes 8.2 ± 1.8 mm . Following randomization treatment groups, either vehicle ACP ivt injected continued every 4 weeks, total four treatments. Sixteen weeks area vehicle‐treated 18.9 6.6 , whereas ACP‐treated 11.4 4.0 reduction by about 36%. Increased, followed decreased, overall thickness OCT following administration. Treatment did not change alter thinning. Geographic atrophy‐like lesions expand are current macaque could be utilized further explore mechanism AMD develop more novel therapeutics.

Language: Английский

Molecular Mechanisms Underlying Heart Failure and Their Therapeutic Potential DOI Creative Commons
Oveena Fonseka, Sanskruti Ravindra Gare, Xinyi Chen

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 324 - 324

Published: Feb. 20, 2025

Heart failure (HF) is a prominent fatal cardiovascular disorder afflicting 3.4% of the adult population despite advancement treatment options. Therefore, better understanding pathogenesis HF essential for exploring novel therapeutic strategies. Hypertrophy and fibrosis are significant characteristics pathological cardiac remodeling, contributing to HF. The mechanisms involved in development remodeling consequent multifactorial, this review, key underlying discussed. These have been divided into following categories thusly: (i) mitochondrial dysfunction, including defective dynamics, energy production, oxidative stress; (ii) lipotoxicity; (iii) maladaptive endoplasmic reticulum (ER) (iv) impaired autophagy; (v) inflammatory responses; (vi) programmed cell death, apoptosis, pyroptosis, ferroptosis; (vii) endothelial dysfunction; (viii) contractility. Preclinical data suggest that there merit targeting identified pathways; however, their clinical implications outcomes regarding treating need further investigation future. Herein, we introduce molecular pivotal onset progression HF, as well compounds related potential preventing or rescuing This, therefore, offers an avenue design discovery therapies

Language: Английский

Citations

1

Sodium Iodate-Induced Ferroptosis in Photoreceptor-Derived 661W Cells Through the Depletion of GSH DOI Open Access
Chao Chen, Han Wang,

Jiuyu Yang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2334 - 2334

Published: March 5, 2025

Oxidative stress-induced photoreceptor cell death is closely associated with the etiology of age-related macular degeneration (AMD), and sodium iodate (SI) has been widely used as an oxidant stimulus in AMD models to induce retinal pigment epithelium (RPE) death. However, mechanism underlying SI-induced remains controversial unclear. In this study, we elucidate that ferroptosis a critical form induced by SI photoreceptor-derived 661W cells. disrupts system Xc-, leading glutathione (GSH) depletion triggering lipid peroxidation, thereby promoting Additionally, enhances intracellular Fe2+ levels, which further facilitates reactive oxygen species (ROS) accumulation, making cells more susceptible ferroptosis. Exogenous GSH, well specific inhibitors such Fer-1 antioxidants like NAC, significantly attenuate These findings provide new insights into mechanisms key pathway

Language: Английский

Citations

1

Retinal Protective Effect of Mono-Ethyl Fumarate in Experimental Age-Related Macular Degeneration via Anti-Oxidative and Anti-Apoptotic Alterations DOI Open Access

Hara Lee,

Siqi Zhang,

Hong Ryul Ahn

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1413 - 1413

Published: Feb. 7, 2025

Age-related macular degeneration (AMD) is a leading cause of vision impairment in people over the age 60. Currently, FDA-approved drugs for AMD have various side effects, and there notable lack drug development dry AMD. This study aimed to explore therapeutic effects mono-ethyl fumarate (MEF) on MEF effectively protected ARPE-19 cells from cell death induced by combination A2E blue light exposure. In C57BL/6J mouse model retinal caused sodium iodate, played role preserving thickness maintaining layered structure retina. It was assessed via fundus imaging, optical coherence tomography, hematoxylin eosin staining. Treatment with significantly increased expression antioxidant proteins such as HO-1, NQO1, SOD1 cells. Additionally, treatment levels GPX4 Concurrently, it reduced apoptosis-related factors, Bax/Bcl-2 ratio Caspase -3 cleavage. These findings suggest that may represent promising candidate management

Language: Английский

Citations

0

Jujing Formula Protects Retinal by Regulating Nrf2/Ho-1 Pathways and Sphingolipid Rheostat and its Key Protein Levels on Liver-Kidney Yin Deficient Retinal Damage Mice DOI
Chong Qi, X.‐S. Wang, Zhe Zhang

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0

Regulated cell death in age-related macular degeneration: regulatory mechanisms and therapeutic potential DOI Creative Commons
Lele Zhang,

Jia-Mei Yu,

Zhaochuan Fan

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown, P. 101285 - 101285

Published: March 1, 2025

Language: Английский

Citations

0

Buspirone Enhances Cell Survival and Preserves Structural Integrity during Oxidative Injury to the Retinal Pigment Epithelium DOI Creative Commons
Manas R. Biswal,

Ryan J. Paulson,

Riddhi Vichare

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(12), P. 2129 - 2129

Published: Dec. 17, 2023

Chronic oxidative stress impairs the normal functioning of retinal pigment epithelium (RPE), leading to atrophy this cell layer in cases advance age-related macular degeneration (AMD). The purpose our study was determine if buspirone, a partial serotonin 1A (5-HT1A) receptor agonist, protected against stress-induced changes RPE. We exposed differentiated human ARPE-19 cells paraquat induce damage culture, and utilized mouse model with sodium iodate (NaIO3)-induced injury evaluate effect buspirone. To investigate buspirone’s on protective gene expression, we performed RT–PCR. Cellular toxicities junctional abnormalities due induction impact were assessed via WST-1 assays ZO-1 immunostaining. used spectral-domain optical coherence tomography (SD-OCT) immunostaining RPE/choroid for structural analysis. showed dose-dependent protection viability buspirone-treated culture preservation RPE integrity under conditions. In NaIO3 model, daily intraperitoneal injection (i.p.) buspirone (30 mg/kg) 12 days improved survival photoreceptors compared those vehicle-treated eyes. ZO-1-stained flat-mounts revealed from mice, as well buspirone-induced Nqo1, Cat, Sqstm1, Gstm1, Sod2 genes untreated Since is implicated pathogenesis AMD, repurposing which currently approved treatment anxiety, might be useful treating or preventing dry AMD.

Language: Английский

Citations

7

Deletion of the stress response protein REDD1 prevents sodium iodate-induced RPE damage and photoreceptor loss DOI Creative Commons
Sandeep Subrahmanian,

Esma I. Yerlikaya,

Siddharth Sunilkumar

et al.

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 5, 2024

Language: Английский

Citations

2

Melanin‐Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age‐Related Macular Degeneration DOI

Keke Huang,

Hongkuan Deng,

Shuang Wang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(30)

Published: Aug. 11, 2024

Ferrous ion accumulation and lethal oxidative stress mediate irreversible retinal pigment epithelial (RPE) cell ferroptosis subsequent photoreceptor degeneration, a potential key pathogenic factor in the onset of dry age-related macular degeneration (dAMD), causing vision loss global elderly population. However, currently, no effective interventional treatment strategy exists clinical practice. Herein, lesion site-targeted melanin-like nanoparticles, named ConA-MelNPs, are designed as novel inhibitor for degenerative diseases. ConA-MelNPs possessed chelating iron characteristics, alleviating severe mitochondrial damage caused by protecting RPE cells from induced sodium iodate (NaIO

Language: Английский

Citations

2

The protective role of Cordyceps cicadae and its active ingredient myriocin against sodium iodate-induced age-related macular degeneration via an anti-necroptotic TNF-RIPK1/3 pathway DOI

Shao Zhuang,

Shi Dong,

Zong Yuan Zhou

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 334, P. 118565 - 118565

Published: July 14, 2024

Language: Английский

Citations

1

Complement C3 knockout protects photoreceptors in the sodium iodate model DOI
Tan Wang, Ying Song, Brent A. Bell

et al.

Experimental Eye Research, Journal Year: 2024, Volume and Issue: unknown, P. 110161 - 110161

Published: Nov. 1, 2024

Language: Английский

Citations

1