bims-mideyd 2026-02-01 papers

Front Cell Dev Biol. 2025 ;13 1739620

Degradable fibrin hydrogels for transplantation of iPSC-derived retinal pigment epithelial cell monolayers.

Alan D Marmorstein, Brittni A Scruggs, Travis Knudsen, Matthew Hill, Francesca N Kopp, Emma Trncic, David Korda, Evan Atherton, Aubrey Berger, Silvia C Finnemann, Jarel Gandhi, Raymond Iezzi.

Death or dysfunction of retinal pigment epithelium (RPE) cells occurs in age-related macular degeneration (AMD) and certain inherited retinal dystrophies (IRDs). Induced-pluripotent stem cell (iPSC) derived-RPE have been used in early-stage clinical trials to treat AMD and IRDs by injecting them as a cell suspension or monolayers. While RPE transplant shows therapeutic potential, issues ranging from failure to repopulate the entire treatment area, clumping and monolayer folding, and a foreign body response to the support have been reported. We've shown that RPE can be grown on high concentration (>30 mg/mL) degradable fibrin hydrogels, and that cell free fibrin hydrogels implanted in the subretinal space degrade without causing inflammation. Here we describe manufacture and surgical implantation of degradable fibrin hydrogels carrying iPSC-RPE into a porcine model of geographic atrophy (GA). Large (15.25 × 58.42 × 0.2 mm) fibrin gel blanks were produced by injection molding, and iPSC-RPE were grown on their surface. Using a mechanical punch, the blank was subdivided into 1.5 × 5.0 × 0.2 mm doses, which fit a custom tool used for storage and surgical placement. Following aseptic packaging, RPE and gels were stable at 37 °C for at least 7 weeks. When transplanted into a pig model of GA, the fibrin scaffold degraded in <1 month and the iPSC-RPE provided partial rescue from GA as assessed by preservation of photoreceptors and blood flow in the choriocapillaris. We conclude that iPSC-RPE delivered on degradable fibrin hydrogels represent a potentially safe and effective approach to RPE transplantation.

Keywords: fibrin; geographic atrophy; iPSCs; retinal pigment epithelium; scaffold; stem cells

DOI: https://doi.org/10.3389/fcell.2025.1739620

Biomolecules. 2026 Jan 12. pii: 131. [Epub ahead of print]16(1):

Protective Effects of Cord Blood Serum (CBS) on Retinal Pigment Epithelium (ARPE-19) and Retinal Photoreceptor-like (661W) Cell Line Viability Under In Vitro Oxidative Stress.

Ilenia Motta, Francesca Corsi, Ilaria Piano, Silvia Bisti, Elisa Bergantin, Marina Buzzi, Maria Claudia Gargini, Piera Versura.

Neuroprotection represents a promising approach for mitigating retinal degeneration. Cord blood serum (CBS), rich in trophic factors such as the brain-derived neurotrophic factor (BDNF), has shown therapeutic potential for ocular surface diseases; however, its role in retinal neuroprotection remains underexplored. This study evaluates the protective effects of CBS on retinal pigment epithelium (ARPE-19) and photoreceptor-like (661W) cells exposed to oxidative stress. Cells were cultured in media supplemented with fetal bovine serum (FBS) or CBS with either high (CBS-H) or low (CBS-L) BDNF content. Oxidative stress was induced using hydrogen peroxide (H2O2), and cell viability was measured via an MTS assay. ZO-1 expression was analyzed in ARPE-19 cells to assess tight junction integrity, while mitochondrial function in 661W cells was examined using MitoRed staining. TrkB receptor involvement was investigated using the inhibitor K252a and Western blot analysis. CBS significantly improved cell viability under oxidative conditions. CBS-H increased ZO-1 expression in ARPE-19 cells, indicating preserved epithelial integrity. In 661W cells, CBS maintained mitochondrial integrity and enhanced TrkB phosphorylation, while TrkB inhibition reduced its protective effect. These findings indicate that CBS confers neuroprotection through BDNF-TrkB signaling together with other trophic factors, supporting its potential as a multifactorial therapeutic strategy for retinal degeneration that deserves further exploration.

Keywords: brain-derived neurotrophic factor (BDNF); cord blood serum; neuroprotection; oxidative stress; retina photoreceptor-like (661W) cells; retina pigment epithelium (ARPE-19) cells

DOI: https://doi.org/10.3390/biom16010131

FASEB Bioadv. 2026 Jan;8(1): e70067

Diabetes Induces Accumulation of Carbonylated Proteins in the Rat Retinal Pigment Epithelium Independently of Oxidative Stress.

Elena Morales-Ramírez, Juan David Villeda-González, Gustavo Sánchez-Chávez, Rocío Salceda.

Diabetic retinopathy (DR) is a major complication of diabetes mellitus. Growing evidence shows that hyperglycemia causes not only microvascular damage but also retinal neural dysfunction. Although different metabolic pathways have been implicated, the exact mechanism behind retinal degeneration remains unclear. Hyperglycemic stimuli have been shown to reduce the function of the retinal blood-barrier (BRB) in both diabetic humans and animals. As part of the BRB, the retinal pigment epithelium (RPE) plays a key role in retinal function by regulating the flow of metabolites and ions between the choroidal blood supply and the outer retina, and by supporting photoreceptor cell functions. Therefore, RPE dysfunction can lead to retinal injury. To understand the role of RPE in DR, we studied oxidative stress in the RPE at the early onset of streptozotocin-induced diabetes in rats. We found a 60% increase in lipoperoxidation at 45 days of diabetes, along with a 50% reduction in ascorbic acid content. Oxidized proteins were significantly increased after 20 and 45 days of diabetes induction, and changes in cell-cell contacts were observed. Despite these findings, superoxide dismutase activity was greatly increased at 45 days of diabetes, while Nrf2 expression and levels of total and reduced glutathione, key regulators of cellular antioxidant capacity, were similar in control and diabetic rat RPE. Moreover, the increase in oxidized proteins was not affected by the antioxidant quercetin nor by the NOS inhibitor L-NAME. These findings suggest that protein carbonylation may impair protein function or turnover, which in turn leads to RPE damage.

Keywords: Nrf2; antioxidant; carbonylation; glutathione; hyperglycemia; oxidative stress; retinal pigment epithelium

DOI: https://doi.org/10.1096/fba.2025-00230

Indian J Ophthalmol. 2026 Feb 01. 74(2): 240-249

650 nm red light enhances aldehyde dehydrogenase 3A1 expression in retina pigment epithelial cells in vitro and in vivo.

Lijun Dong, Hui Qi, Gaoen Ma, Zhihong Lin, Zhengyang Tao, Zefeng Kang, Yanxian Chen, Mingguang He, Hetian Lei, Hongwei Deng.

PURPOSE: Low-dose 650 nm red light has been found to slow myopia progression, although the underlying mechanisms remain unclear. This study aimed to investigate its antioxidative effects and molecular pathways.
METHODS: An oxidative stress model was established in ARPE-19 cells by treatment with hydrogen peroxide (H₂O₂) at concentrations of 0, 0.5, and 0.75 mM. The cells were then irradiated with red light for 9 minutes, twice daily for 2 days, with an equivalent-power white light group serving as a control. Following irradiation, oxidative stress was quantified using a DCFH-DA assay, and DNA damage was assessed by γ-H2AX immunofluorescence. For the in vivo study, mice received ocular irradiation with red light (9 minutes/session, twice daily for 5 days) using a white light-exposed group as a control. Changes in axial length were measured post irradiation using anterior segment optical coherence tomography. Subsequently, retinal pigment epithelial (RPE) cells were isolated from the mice for RNA sequencing to analyze differential mRNA expression. Quantitative real-time PCR (qPCR) and Western blotting were employed to validate the expression of specific genes associated with ocular diseases.
RESULTS: At a concentration of 0.75 mM hydrogen peroxide, red light irradiation significantly reduces oxidative stress levels compared to the control group. RNA sequencing data revealed that there were 274 genes upregulated and 225 genes downregulated in RPE cells from mouse eyes illuminated with the 650 nm red light. The gene encoding aldehyde dehydrogenase 3A1 (ALDH3A1), which is significantly upregulated after red light irradiation, plays an important role in protecting ocular structures from oxidative damage. qPCR and Western blot analyses confirmed that ALDH3A1 was heightened in RPE cells from mouse eyes in vivo and in cultured human RPE cells in vitro illuminated by the 650 nm red light.
CONCLUSIONS: ALDH3A1 may play a part in myopia improvement upon 650 nm red light illumination.

Keywords: Aldehyde dehydrogenase 3A1; RNA sequencing; myopia; red light

DOI: https://doi.org/10.4103/IJO.IJO_1594_25