bims-mideyd 2026-04-26 papers

Biomed Mater. 2026 Apr 24.

A tunable, biofabricated light-delivery platform for in vitro modelling of age-related macular degeneration using iPSC-derived RPE cells.

Anwar Azad Palakkan, Gowthami Shankar, T P Vignesh, Ramasamy Kim.

The lack of physiologically relevant and controllable experimental systems has limited mechanistic understanding of age-related macular degeneration (AMD) and the development of effective therapeutic strategies. Here, we present a tunable in vitro retinal pigment epithelium (RPE) stress model that integrates engineered light delivery with lipid modulation to reproduce early AMD-like cellular pathology under standard culture conditions. Human RPE cells (ARPE-19 and iPSC-derived RPE) were exposed to precisely controlled, low-intensity light-induced oxidative stress in the presence of docosahexaenoic acid (DHA), a highly unsaturated retinal lipid, or palmitic acid (PA) as a saturated lipid control. Cellular responses were assessed using functional and structural readouts including lysosomal and mitochondrial activity, membrane integrity, epithelial morphology, tight junction organization, and lipid peroxidation. A programmable LED-based exposure system enabled fine control over light intensity, duration, and cycling, allowing delivery of sub-lethal, chronic oxidative stress. Combined light and DHA exposure selectively induced lipid peroxidation, disruption of ZO-1-defined tight junctions, and progressive loss of RPE viability, while PA-treated cells and non-retinal HuH7 hepatocytes showed minimal sensitivity. ARPE-19 cells responded rapidly, whereas iPSC-derived RPE cells exhibited delayed but comparable pathological changes, reflecting differences in cellular maturity and stress resilience. Pharmacological inhibition of ferroptosis using ferrostatin-1 significantly reduced lipid peroxidation and rescued epithelial integrity and cell viability, identifying ferroptosis as a key mechanism underlying RPE vulnerability in this system. By enabling programmable and reproducible delivery of oxidative lipid stress, this modular light-based platform provides a biofabrication-compatible framework for modeling early AMD, with potential for integration into more complex retinal constructs, co-culture systems, and high-throughput therapeutic screening pipelines.

Keywords: Age Related Macular Degeneration; DHA, docosahexaenoic acid; Ferroptosis; Light; RPE; iPSC-derived RPE

DOI: https://doi.org/10.1088/1748-605X/ae6498

Exp Eye Res. 2026 Apr 21. pii: S0014-4835(26)00190-9. [Epub ahead of print]268 111034

Differential protective effects of blue light (BL)-exposed retinal pigment epithelial cells by selective BL-filtering lenses.

Mohamed Abdouh, William Sebag, Nadia Abdouh, Alicia Goyeneche, Miguel N Burnier.

Blue light (BL) is harmful to eye posterior segment structures. It induces accelerated retina aging and the progression of retinal diseases. We reported that BL is cytotoxic to retinal pigment epithelial (RPE) cell through oxidative damage. Herein, we investigated the potential of selective BL-filtering intraocular lenses (BL-IOL) to mitigate these deleterious effects. Human RPE cells were exposed to BL in the absence or presence of a panel of BL-IOLs having different pigment compositions and BL-filtering potentials. Cells were analyzed for their oxidative status (levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨM)), and growth (proliferation, metabolic activity and viability). Exposure of RPE cells to BL significantly increased the levels of cellular ROS and mitochondrial superoxide anion. While these effects did not affect cell proliferation, they triggered a collapse of the ΔΨM, a decrease in cell metabolic activity and an increase of cell death. Independent of the BL-IOL used in the BL beam, there was a drop in oxidative stress and ensuing protection of cells from the BL-mediated cytotoxic effects. Notably, BL-IOL with higher filtration potential of high-energy BL provided better photoprotection to exposed cells. This study highlights the need to selectively filter BL radiation wavelengths from light reaching the eye. It will help to define the best filtering devices to prevent RPE cell damage and eye posterior segment structure-related disease progression, such as during age-related macular degeneration.

Keywords: Blue light; Blue light filtration; Cytotoxicity; In vitro; Oxidative stress; Retinal pigment epithelial cells

DOI: https://doi.org/10.1016/j.exer.2026.111034

FEBS Open Bio. 2026 Apr 24.

Derivation and characterization of retinal pigment epithelium from urine-derived iPSCs.

Daniella Beiner, Hainan Zhu, Carol Christine Bosholm, Heuy-Ching Wang, Tracy Criswell, Anthony Atala, Jian-Xing Ma, Yuanyuan Zhang.

Age-related macular degeneration (AMD), particularly its dry form, is a leading cause of irreversible vision loss due to retinal pigment epithelium (RPE) dysfunction and loss. Addressing this unmet therapeutic need requires non-invasive strategies for generating patient-specific RPE cells. This study reports the successful generation and initial characterization of RPE cells derived from urine-derived induced pluripotent stem cells (u-iPSC-RPE). Urine-derived stem cells (USCs) were isolated from healthy individuals and comprehensively characterized, confirming strong expression of renal progenitor makers and mesenchymal stem cell markers, while lacking standard hematopoietic markers. USCs were reprogrammed into iPSCs using the integration-free Sendai virus expressing the Yamanaka factors. The reprogrammed u-iPSC clones displayed characteristic pluripotency marker expression and demonstrated clearance of the Sendai virus by later passages. Subsequently, these u-iPSCs were efficiently differentiated into RPE cells, exhibiting characteristic hexagonal morphology and pigmentation which was confirmed by the expression of key RPE-specific proteins. Our findings demonstrate the feasibility and reliability of generating patient-specific u-iPSC-RPE cells from readily accessible USCs providing a foundation for future studies to investigate their functional potential for retinal disease modeling and therapeutic applications for AMD.

Keywords: age‐related macular degeneration; cell therapy; induced pluripotent stem cells; regenerative medicine; retinal pigment epithelium; urine‐derived iPSC; urine‐derived stem cells

DOI: https://doi.org/10.1002/2211-5463.70246

Exp Eye Res. 2026 Apr 19. pii: S0014-4835(26)00188-0. [Epub ahead of print] 111032

Genome-Wide CRISPR Knockout Screening Identifies Novel Disease-Associated Genes in Retinal Pigment Epithelium Cells.

Rui Li, Lei Xie, Jing Hu, Bei Liu, Haijiang Zhang, Hao Qian.

Dysfunction and degeneration of retinal pigment epithelium (RPE) cells are common pathological features observed in various retinal degenerative diseases. It has been proposed to treat these diseases by either protecting RPE cells or replacing them with new RPE cells derived from stem cells. However, the development of effective therapeutic strategies is still limited due to the insufficient understanding of the pathogenic factors involved in retinal degeneration and their impact on the function and survival of RPE cells. In this study, we employed genome-scale CRISPR knockout (KO) screening in human RPE cells to identify genes critical for RPE cell survival. Over 300 genes were identified, including well-established housekeeping genes as well as several candidate genes previously linked to retinal degeneration, many of which still lack comprehensive investigation. Among these, we further validated PRPF38B, which was both enriched in our screening and highlighted in a prior family-based linkage study, as essential for RPE cell survival, thus confirming the effectiveness of our approach. As a component of the spliceosome, we found that PRPF38B is crucial for functions specific to RPE cells, offering new insights into its role in retinal degeneration. Our study presents a novel approach for investigating risk genes associated with retinal diseases and may inspire future research on RPE cells and vision disorders.

Keywords: CRISPR Screening; PRPF38B; RPE cell; Retinal Degeneration; Retinitis Pigmentosa

DOI: https://doi.org/10.1016/j.exer.2026.111032

Sci Rep. 2026 Apr 20.

Oxidative stress promotes the progression of age-related macular degeneration by up-regulating Spp1 to activate the JAK/STAT signaling pathway.

Qi Zeng, Xingyu Hua, Yutong Liu, Sha Wang.

Keywords: Age-related macular degeneration; JAK-STAT signaling pathway; Oxidative stress; Retinal pigment epithelium cells; Secreted phosphoprotein 1

DOI: https://doi.org/10.1038/s41598-026-48556-6