bims-mideyd 2026-05-31 papers

Exp Eye Res. 2026 May 27. pii: S0014-4835(26)00246-0. [Epub ahead of print]270 111090

Mitochondrial transplantation protects the retinal pigment epithelial cells from the oxidative stress induced by NaIO3.

Yeon-Jin Heo, Kausik Bishayee, Joo Yeon Jhun, Se Gyeong Han, Yeon Su Lee, Young Gun Park, Mi-La Cho, Yong Soo Park.

The retinal pigment epithelium (RPE) is the outermost part of the retina, and it is essential for the photoreceptor survival and function. Oxidative stress, aging, accumulation of lipofuscin, and drusen can lead to retinal degenerative diseases such as age-related macular degeneration (AMD). Those stress conditions increase reactive oxygen species (ROS) levels and oxidative stress, which can induce mitochondrial dysfunction and promote RPE cell death during retinal degeneration. We transplanted mitochondria, isolated from C2C12 cells, into cultured RPE cells, and RPE cell injury was induced by NaIO3 treatment. To evaluate the protective effect of mitochondrial transplantation, Annexin V/PI and cell viability assays were performed to measure the cell survival, and ROS levels were measured by flow cytometry to analyze cellular stress. To understand the underlying protective mechanism of mitochondrial transplantation, we measure expression of the antioxidant genes, mitochondrial fusion/fission markers, and mitophagy makers using qRT-PCR and Western blot methods. Mitochondrial transplantation reduced NaIO3-induced cell death and ROS levels, and antioxidant genes related to the Nrf2 pathway were upregulated, providing a protective effect against retinal damage. In addition, mitochondrial fusion was increased, whereas fission was decreased in the NaIO3 model. Furthermore, mitophagy was increased by mitochondrial transplantation, which could clear damaged mitochondria through a cellular protective pathway. In conclusion, mitochondrial transplantation could protect the RPE cells by maintaining mitochondrial homeostasis and promoting the antioxidant pathway via Nrf2 activation. This study suggests that mitochondrial transplantation could be a potential treatment option for improving AMD progress in the future.

Keywords: Mitochondrial transplantation; Mitophagy; Nrf2; ROS; Retinal pigment epithelium

DOI: https://doi.org/10.1016/j.exer.2026.111090

Antioxidants (Basel). 2026 May 20. pii: 647. [Epub ahead of print]15(5):

Non-Erythropoietic EPO (EPO-R76E) Protects RPE Cells from Ferroptosis by Modulating the Labile Iron Pool and NRF2-GPX4 Axis.

Sundaramoorthy Gopi, George T Prodanoff, Christopher L Passaglia, Mark S Kindy, Vijaykumar Sutariya, Ganesh V Halade, Alfred S Lewin, Manas R Biswal.

Retinal pigment epithelium (RPE) degeneration remains a formidable challenge in dry age-related macular degeneration (AMD) research, primarily due to the toxic interplay between iron overload and ferroptosis. We investigated whether EPO-R76E, a non-erythropoietic modified variant of erythropoietin, could effectively interrupt this destructive cycle. Using ARPE-19 cells challenged with ferric ammonium citrate (FAC) to model iron-induced toxicity, we show that EPO-R76E confers protection against ferroptosis. Our results demonstrate that this variant significantly reduces the intracellular labile iron pool, directly quenching the lipid peroxidation that drives ferroptotic cell death. This resilience is fueled by a robust upregulation of Glutathione Peroxidase 4 (GPX4) and the broad transcriptional activation of the NRF2 (Nuclear factor erythroid 2-related factor 2) NRF2 antioxidant axis. Furthermore, we found that EPO-R76E enhances autophagic flux, ensuring that cells maintain essential proteostasis and "housekeeping" functions even under metabolic crisis. By integrating iron sequestration with reinforced antioxidant signaling and cellular clearing mechanisms, EPO-R76E stands out as a potent candidate for preserving RPE health. These findings uncover a novel molecular framework for protecting the retina against iron-mediated injury, positioning EPO-R76E as a versatile and targeted gene-based therapeutic for addressing the fundamental causes of retinal degeneration.

Keywords: Epo-R76E; GPX4; LC3B; NRF2 signaling; age-related macular degeneration (AMD); antioxidants; autophagy; ferric ammonium citrate (FAC); ferroptosis; gene therapy; iron homeostasis; labile iron pool; lipid peroxidation; modified variant of erythropoietin; neuroprotection; oxidative stress; p62/SQSTM1; retinal pigment epithelium (RPE)

DOI: https://doi.org/10.3390/antiox15050647

Int J Ophthalmol. 2026 ;19(6): 1048-1056

Fructus lycii mitigates oxidative stress in dry age-related macular degeneration models via Nrf2/ARE pathway.

Yuan Peng, Ling-Yan Liang, Han-Lei Wei, Qin Huang, Ling-Mei Yuan, Yu-Yan Xie, Qiu-Yu Tang, An-Qi Wang, Jia-Ming Li, Qin-Shang Guo, Bing-Lin Huang.

AIM: To evaluate the effect of Fructus lycii (FL) aqueous extract on dry age-related macular degeneration (AMD) in mice via the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway and investigate the protective effect of FL-containing serum on hydrogen peroxide (H2O2)-treated human retinal pigment epithelial cells (ARPE-19) in vitro.
METHODS: In vivo dry AMD mouse model was established by intraperitoneal injection of NaIO3 solution and treated with aqueous extract of FL. The pathological changes of mouse retinal tissues were observed by electron microscopy; the activity of superoxide dismutase (SOD) and catalase (CAT) in mouse serum was detected by colorimetric method. In vitro dry AMD model was established by H2O2 induction of ARPE-19 cells and treated with FL-containing serum. Methylthiazolyldiphenyl-tetrazolium bromide assay and scratch assay were performed to detect cell activity and proliferation ability. Expression of Nrf2, heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) in retinal tissues and ARPE-19 cells were detected by Western blot and quantitative real-time polymerase chain reaction (Q-PCR).
RESULTS: The in vivo study revealed severe deposits under the retinal pigment epithelium and thickened Bruch's membrane in dry AMD mice. However, aqueous extract of FL reduced the formation of deposits and decreased the thickness of Bruch's membrane. SOD and CAT activities were significantly reduced in the serum of dry AMD mice, and aqueous extract of FL upregulated SOD and CAT activities. In addition, gene and protein expression of Nrf2, HO-1, and GCLC were significantly downregulated in dry AMD mice, but significantly upregulated by FL aqueous extract treatment. In vitro studies showed that H2O2 inhibited the activity and proliferative capacity of ARPE-19 cells and downregulated the protein and gene expression of Nrf2, HO-1 and GCLC. However, in H2O2-treated ARPE-19 cells, FL-containing serum not only increased cell activity and proliferative capacity, but also upregulated protein and gene expression of Nrf2, HO-1, and GCLC.
CONCLUSION: FL reduces oxidative stress in an animal model of dry AMD through the Nrf2/ARE signaling pathway and has a protective effect on dry AMD in vitro and in vivo, providing new insights into the therapeutic use of FL for dry AMD.

Keywords: Fructus lycii aqueous extract; Nrf2/ARE pathway; dry age-related macular degeneration; oxidative stress

DOI: https://doi.org/10.18240/ijo.2026.06.04

Biomolecules. 2026 Apr 24. pii: 635. [Epub ahead of print]16(5):

Prominin-1 and Retinal Degenerative Disorders: Expanding the Biology from Photoreceptors to the Retinal Pigment Epithelium.

Sujoy Bhattacharya, Caitlin Ang, Megan Soucy, Stephen H Tsang, Edward Chaum.

Prominin-1 (Prom1/CD133) has long been recognized as a structural determinant of photoreceptor outer segment (OS) morphogenesis, yet rapidly accumulating evidence extends its role to retinal pigment epithelium (RPE) homeostasis, encompassing autophagy-lysosomal flux, outer segment phagocytosis, mitochondrial function, and regulation of inflammatory stress. This review synthesizes mechanistic and transcriptomic insights that position PROM1 as a central regulator of photoreceptor and RPE integrity, reframing Prom1 disease as a multi-compartment retinal disorder relevant to both inherited retinal dystrophies (IRDs) and atrophic age-related macular degeneration (aAMD). We develop a dual-axis conceptual model in which Prom1 dysfunction can initiate pathology in either the photoreceptors (OS morphogenesis failure) or the RPE, including impaired autophagic flux, lysosomal activity, defective phagocytosis, and Epithelial-Mesenchymal Transition (EMT)-like de-differentiation, with secondary cross-compartmental degeneration. Clinically, autosomal-dominant missense variants associate with macular or cone-rod dystrophy, whereas biallelic truncating/splice-site mutations drive early-onset rod-cone disease and panretinal/RPE atrophy, illustrating genotype-phenotype diversity. By integrating recent high-resolution transcriptomic data from Prom1-deficient RPE cells with long-standing insights into photoreceptor biology, we highlight converging pathways of degeneration that challenge a photoreceptor-centric view and unify disparate phenotypes within a single molecular framework. These insights broaden the therapeutic landscape, advancing gene augmentation and pathway-targeted strategies to preserve RPE integrity, sustain photoreceptor function, and modify disease course in PROM1-associated IRDs and atrophic AMD.

Keywords: atrophic age-related macular degeneration; autophagy; epithelial–mesenchymal transition; inherited retinal dystrophy; lysosome; mitochondrial function; partial EMT; phagocytosis

DOI: https://doi.org/10.3390/biom16050635