bims-mideyd 2026-03-22 papers

Mol Biol Rep. 2026 Mar 18. pii: 507. [Epub ahead of print]53(1):

Gypenosides mitigate acrylamide-induced oxidative stress, inflammation and lipid metabolic dysregulation in retinal pigment epithelial cells and in zebrafish embryos.

Gabriel Mbuta Tchiveleketea, Michal R Baran, Manuel Evaristo Augusto Vilengalenga, Sebastião Tumitânguab, James Reilly, Xinhua Shua.

BACKGROUND: Acrylamide (ACR) is an environmental and dietary contaminant widely known to induce imbalance in several biological systems, including oxidative stress, inflammation, and metabolic dysregulation. This study investigated the protective effects of gypenosides (GYP) against ACR-induced toxicity in human retinal pigment epithelial (RPE) cells and zebrafish embryos.
METHODS AND RESULTS: RPE cells and zebrafish embryos were treated with ACR, or ACR + GYP; the levels of reactive oxygen species (ROS), antioxidative enzymes, proinflammatory cytokines, and lipids were measured using biochemical approaches. Our findings demonstrate that ACR exposure significantly elevated ROS production, increased lipid peroxidation, suppressed antioxidant defences, and upregulated pro-inflammatory cytokines in RPE cells. Additionally, ACR disrupted lipid metabolism, significantly increasing cellular cholesterol, triglyceride, and phospholipid levels while altering cholesterol metabolism gene expression. Co-treatment with GYP effectively mitigated ACR-induced oxidative stress by normalising ROS levels, restoring antioxidant enzyme activities, and upregulating antioxidant gene expression. GYP also attenuated the ACR-triggered inflammatory response, significantly downregulating the expression of proinflammatory cytokine genes. Furthermore, GYP normalised lipid profiles and modulated lipid-related gene expression disrupted by ACR exposure. Parallel zebrafish experiments corroborated these protective effects. ACR exposure led to delayed hatching, impaired cardiac function, increased ROS production, and neutral lipid accumulation. These adverse effects were markedly ameliorated by GYP co-treatment, which reduced oxidative stress, downregulated proinflammatory markers, and restored lipid homeostasis.
CONCLUSION: The results highlighted that GYP, as a natural protective agent against ACR-induced cellular and metabolic toxicity in both in vitro and in vivo models, exhibited antioxidative, anti-inflammatory, and lipid-regulatory properties.

Keywords: Acrylamide; Gypenosides; Inflammation; Oxidative stress; Retinal pigment epithelial cells; Zebrafish embryos

DOI: https://doi.org/10.1007/s11033-026-11676-3

Cytoskeleton (Hoboken). 2026 Mar 15. e70128

Arp2/3 Inhibition Suppresses Membrane Dynamics but Does Not Block Pigment Granule Migration in Isolated Fish Retinal Pigment Epithelial (RPE) Cells.

Keelan O'Reilly, Taiki Tashiro, Kristina Kristo, Christina King-Smith.

The retinal pigment epithelium (RPE) lies at the back of the vertebrate eye and plays important roles in vision. In the eyes of fish, which lack dilatable pupils, RPE pigment granules undergo massive migrations to regulate light intensity. Previous work has demonstrated that both aggregation and dispersion of pigment granules through apical projections of RPE require an intact actin cytoskeleton. To determine the role of the actin-nucleating complex, Arp2/3, on pigment granule movement, isolated RPE cells were treated with the inhibitors CK-666 and CK-869. Both drugs caused a reversible rapid cessation of both lateral and distal membrane extension of the cells' apical projections, resulting in an overall thinning of the projections. CK-666 also stimulated the formation of F-actin aggregates in projections, mainly at the distal tips. Despite these structural changes, these inhibitors had no effect on pigment granule aggregation or dispersion. Immunolocalization of Arp3 showed diffuse fluorescence throughout isolated cells. The actin side-binding protein, tropomyosin, was also present in RPE cells, aligning with F-actin bundles. While it cannot be ruled out that these drugs only partially inhibited Arp2/3 complex nucleation, the results suggest that while actin nucleation by Arp2/3 inhibition is important in membrane dynamics of the RPE apical projections, it is not critical for pigment granule movement.

Keywords: Arp2/3 complex; actin filaments; actin nucleation; melanosomes; pigment granule migration; retinal pigment epithelium

DOI: https://doi.org/10.1002/cm.70128

J Med Food. 2026 Feb;29(2): 91-101

Hot-Air-Dried Eruca sativa Mill. Extracts Prevent Retinal Inflammation and Unfolded Protein Responses in ARPE-19 Cells.

Minseo Cho, Jisu Lee, Yoseob Kim, Young Jun Kim, Caglar Doguer, Misook Kim, Jung-Heun Ha.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) constitute leading causes of irreversible visual impairment; both are pathologically linked to chronic inflammation and endoplasmic reticulum (ER) stress in retinal pigment epithelial (RPE) cells. This study aimed to investigate the protective effects of hot-air-dried Eruca sativa Mill. extract (ESH) on lipopolysaccharide (LPS)- and thapsigargin (Tg)-induced inflammatory and ER stress responses, respectively, in ARPE-19 cells. ESH pretreatment significantly suppressed LPS-induced phosphorylation of nuclear factor kappa B (NF-κB), inhibitor of kappa B alpha, and c-Jun N-terminal kinase, indicating effective inhibition of inflammatory signaling cascades. At the transcriptional level, ESH markedly attenuated the expression of tumor necrosis factor-α mRNA, suggesting downstream prevention of NF-κB-mitogen-activated protein kinase-mediated inflammatory gene activation. Under ER stress conditions, ESH significantly attenuated the upregulation of CCAAT/enhancer-binding protein (C/EBP) homologous protein and X-box binding protein-1, along with reductions in the expressions of cleaved caspase-3 and -9, indicating mitigation of ER stress-associated retinal apoptosis. Additionally, ESH prevented Tg-inducible vascular endothelial growth factor (VEGF) mRNA expression, VEGF protein secretion, and intracellular calcium level. Strong positive correlations were observed between intracellular calcium and VEGF secretion (r = 0.888), and between VEGF mRNA and protein levels (r = 0.843), supporting a potential mechanistic link. Collectively, these findings demonstrate that ESH modulates inflammatory, ER stress, apoptotic, and angiogenic pathways, suggesting its potential as a functional dietary supplement to mitigate RPE dysfunction in AMD and DR.

Keywords: ARPE-19 cells; Eruca sativa Mill; endoplasmic reticulum stress; hot-air drying; inflammation

DOI: https://doi.org/10.1177/1096620X251412888

Invest Ophthalmol Vis Sci. 2026 Mar 02. 67(3): 42

Targeted Ferroptosis Improves RPE Phagocytosis via MERTK/NFE2L2/HMOX1 Axis to Alleviate Retinitis Pigmentosa.

Yuwen Wen, Lujia Feng, Shengsong Xu, Ting Zhang, Zhaohao Huang, Yong Du, Yingting Zhu, Caibin Deng, Ye Deng, Wenru Su, Shaochong Zhang, Yehong Zhuo.

Purpose: Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder in which progressive rod and cone degeneration, together with retinal pigment epithelium (RPE) dysfunction, culminates in vision loss. Given the lack of effective therapies, we investigated RPE pathogenic alterations in RP models to inform potential therapeutic strategies.
Methods: This study integrates Royal College of Surgeons (RCS) rat in vivo and human primary RPE cells in vitro to investigate the RP model. We employ single-cell RNA sequencing (scRNA-seq) to analyze the transcriptional differences in the retinas of RCS and RDY rats and to interrogate ferroptosis-related signal transduction. After treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1) in both in vivo and in vitro RP models, therapeutic efficacy and RPE phagocytic function were assessed by using fundus photography, hematoxylin and eosin staining, electroretinography, Western blotting, immunofluorescence, and reverse transcription quantitative PCR.
Results: Our scRNA-seq revealed marked transcriptional remodeling across retinal cell populations in RCS rats, with ferroptosis-related programs evident in most cell types and most pronounced in RPE. NFE2L2 and HMOX1 were significantly upregulated in RCS rats and in vitro MERTK-deficient RP models. Fer-1 ameliorated cytoskeletal disorganization and restored RPE phagocytic function, whereas selective silencing of NFE2L2 or HMOX1 reduced iron overload and rescued cytoskeletal integrity and phagocytosis, supporting a pathogenic role for ferroptosis in RP.
Conclusions: Ferroptosis is a critical driver of MERTK-deficient RP, influencing RPE dysfunction through the MERTK/NFE2L2/HMOX1 axis. These insights highlight the potential therapeutic strategy of targeting ferroptosis to regulate RPE function in the treatment of MERTK-deficient RP.

DOI: https://doi.org/10.1167/iovs.67.3.42

Nat Commun. 2026 Mar 18.

Bst2-targeted senotherapy restores visual function by eliminating senescent retinal cells.

Jun Yong Oh, Jae-Byoung Chae, Hyo Kyung Lee, Chul-Woo Park, Minseo Bae, Gyuri Kim, Yujeong Oh, Gyeongseok Yang, Sangpil Kim, Hae Won Ok, Dohyun Kim, Chaekyu Kim, Semin Lee, Jiwon Jang, Hyewon Chung, Ja-Hyoung Ryu.

Senescent cells contribute to degenerative processes in multiple tissues, including the retina. In the retinal pigment epithelium (RPE), their accumulation is closely associated with retinal aging and disease progression. Eliminating senescent RPE cells has shown therapeutic potential, but conventional senolytics often lack the specificity required to spare non-senescent cells, raising safety concerns. To overcome this, we performed integrated transcriptomic analyses of male mouse-derived RPE cells under natural aging and chemically induced senescence conditions. These analyses identified Bst2 as a membrane-localized marker selectively upregulated in senescent RPE cells, with minimal expression in young controls. Based on this discovery, we developed a modular, antibody-pluggable drug delivery platform-B-Z-PON-comprising mesoporous silica nanoparticles functionalized with a recombinant Fc-binding domain and conjugated with anti-Bst2 antibodies. This nanocarrier selectively accumulates in Bst2-expressing senescent RPE cells, enabling targeted drug delivery and sparing healthy retinal cells. In vivo administration of ABT-263-loaded B-Z-PON in aged and senescence-induced retinal degeneration models resulted in the selective ablation of senescent cells, restoration of RPE function, and improved visual outcomes. Together, our study integrates senescence-specific marker discovery with precision nanomedicine, establishing a versatile platform for targeted senotherapy. These findings offer a promising therapeutic approach for retinal aging disorders, such as age-related macular degeneration.

DOI: https://doi.org/10.1038/s41467-026-70797-2