bims-mideyd 2025-10-05 papers

Eur J Pharmacol. 2025 Sep 26. pii: S0014-2999(25)00953-7. [Epub ahead of print]1006 178199

Protective effects of acemannan-enriched Aloe polysaccharide J2 against UVA-induced autophagic cell death in retinal pigment epithelial cells.

Chen-Chun Kao, Uvarani Chokkalingam, Anuma Singh, Pei-Chun Shih, Ekambaranellore Prakash, Jang-Shiun Wang.

Age-Related Macular Degeneration (AMD) is one of the leading causes of irreversible vision loss worldwide, characterized by the degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells, resulting in progressive loss of central vision. RPE cells are highly specialized and essential for retinal function, and their malfunction due to genetic, environmental, or age-related factors contributes significantly to AMD pathogenesis. Ultraviolet A (UVA) radiation is recognized as a major causative factor, as it induces the accumulation of reactive oxygen species (ROS) in RPE cells, ultimately contributing to the development of AMD. On the other hand, acemannan, a D-isomer mucopolysaccharide derived from Aloe vera pulp, is known for its antioxidant and anti-inflammatory properties. In this study, we extracted a highly purified Aloe-derived polysaccharide fraction enriched in acemannan, designated Aloe polysaccharide J2 (ACJ2), to investigate its protective effects against UVA-induced RPE damage. The results showed that post-treatment with ACJ2 significantly reduced UVA-induced cell death by lowering mitochondrial ROS levels, suppressing phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK), and downregulating proinflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and inducible nitric oxide synthase (iNOS). Furthermore, ACJ2 enhanced heme oxygenase-1 (HO-1) expression and mitochondrial DNA levels, and inhibited p62/sequestosome-1 (p62) consumption and microtubule-associated protein 1 light chain 3 (LC3)-I/II conversion, thereby reducing autophagic flux. These findings demonstrate that ACJ2 mitigates UVA-induced damage and restores disrupted autophagy in RPE cells, supporting its potential as a therapeutic candidate for AMD.

Keywords: Aloe polysaccharide; Autophagy; Inflammatory response; Mitochondrial dysfunction; RPE; UVA

DOI: https://doi.org/10.1016/j.ejphar.2025.178199

J Toxicol Sci. 2025 ;50(10): 569-576

Activator protein-1 mediates blue light-induced phototoxicity in retinal pigment epithelial cells.

Jae Rim Lee, Myeong Ryeo Kim, Kwang Won Jeong.

Age-related macular degeneration is a leading cause of vision loss and is characterized by the accumulation of drusen in the retinal pigment epithelium. N-retinylidene-N-retinylethanolamine (A2E), a major component of drusen, induces phototoxicity upon exposure to blue light. Given that blue light activates the MAPK pathway and triggers apoptosis, the present study aimed to determine the role of signaling via the activator protein-1 (AP-1) transcription factor in A2E-laden ARPE-19 cells. RNA-sequencing identified significant upregulation of the UV response and p53 pathways. In silico analysis predicted that JUN was a key upstream transcriptional regulator, and experimental validation confirmed increased JUN phosphorylation and AP-1 target gene expression upon blue light exposure. Furthermore, blue light treatment decreased BCL2 and increased BAX protein levels, thereby promoting apoptosis via caspase activation and PARP cleavage, as also confirmed by flow cytometry. These findings suggest that blue light induces apoptosis via JUN, which activates AP-1 in A2E-laden ARPE-19 cells. The present study provides new insights into the molecular mechanisms underlying blue light-induced retinal damage and its potential contribution to the progression of age-related macular degeneration.

Keywords: AP-1; Apoptosis; Blue light; JUN; Phototoxicity; Retinal pigment epithelium

DOI: https://doi.org/10.2131/jts.50.569

Biomaterials. 2025 Sep 24. pii: S0142-9612(25)00661-1. [Epub ahead of print]327 123742

Development of a biodegradable smooth-surface microcarrier for retinal pigment epithelial cell expansion and maturation.

Zengping Liu, Daniel Soo Lin Wong, Bhav Harshad Parikh, Jian Li, Abdurrahmaan Al-Mubaarak, Hang Liu, Binxia Yang, Mayuri Bhargava, Zibiao Li, Xian Jun Loh, Xinyi Su.

The retinal pigment epithelium (RPE) is essential for the health and function of the retina and, more specifically, the photoreceptors. Hence, the dysfunction of RPE leads to various retinal degeneration diseases. The rising prevalence of these disorders highlights the need for effective, large-scale cell-based therapies, particularly those utilizing stem cell-derived RPE cells. This study presents the development of a biodegradable, smooth surface microcarrier designed to facilitate the expansion and maturation of RPE cells derived from induced pluripotent stem cells (iPSCs). Using a three-dimensional (3D) culture system with polycaprolactone (PCL) porous microcarriers, we demonstrate that RPE cells exhibit comparable adhesion and growth on microcarriers as they do on traditional two-dimensional (2D) culture plates. The microcarrier system facilitates efficient maturation and yields higher quantities of functional RPE cells, highlighting its potential for large-scale production to meet both clinical demands and in vitro large-scale screening studies. Moreover, RPE cells cultured on this microcarrier can be directly frozen and recovered, maintaining their phenotypic and functional integrity upon thawing. This research showcases the scalability and practicality of RPE cell production, providing a robust solution for the storage and delivery of RPE cells. While our results establish the feasibility of direct cryopreservation and recovery of monolayer RPE cells on microcarriers, the designation of a 'ready-to-use' product format is preliminary and will require expanded assessment of long-term functionality, safety, and direct translational outcomes in future studies.

Keywords: Microcarriers; Polycaprolactone; Retinal pigment epithelium; Stem cells

DOI: https://doi.org/10.1016/j.biomaterials.2025.123742

Commun Biol. 2025 Oct 01. 8(1): 1408

Intermittent fasting attenuates glial hyperactivation and photoreceptor degeneration in a NaIO3-induced mouse model of age-related macular degeneration.

Jingzhen Li, Beibei Wang, Pinjie Liu, Xuecheng Qiu, Qiyun Bian, Congxin Shen, Yanyan Li, Mengwen Shao, Meng Li.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss, with limited treatments available. Recent studies suggest intermittent fasting (IF) may offer neuroprotective benefits for aging and age-related disorders, but its efficacy in AMD has not yet been established. Here, using a sodium iodate (NaIO3)-induced AMD model in male mice, we find that pretreatment with an IF diet regimen mitigates NaIO3-induced cellular damage and loss of both retinal pigment epithelium (RPE) and photoreceptors. Visual function tests indicate that IF preserves vision in NaIO3-treated mice. Transcriptome analyses show IF counteracts NaIO3-induced transcriptional dysregulation, affecting genes related to reactive oxygen species (ROS), inflammation, and photoreceptor structure. Further experimental results confirm that IF effectively reduces ROS levels and inhibits the activation of microglia and Muller cells in the retina. Collectively, these findings indicate that IF reduces ROS production and inflammation in NaIO3-induced retinal damage, providing a potential therapeutic strategy for oxidative stress-induced retinal degenerative diseases, including AMD.

DOI: https://doi.org/10.1038/s42003-025-08815-0