bims-mideyd 2025-06-22 papers

Front Pharmacol. 2025 ;16 1545731

Modified ZhuJing pill protects retinal pigment epithelium against oxidative stress-induced epithelial-mesenchymal transition through Nrf2-mediated Akt/GSK3β pathway.

Ning Yang, Caijian Xiong, Siqi Feng, Mengqi Gao, Siqi Zhou, Qinyi Hui, Xin Zhou, Qingzi Jin, Yan Shao, Xinrong Xu.

Background: The modified ZhuJing pill (mZJP) has been widely used in China as a classical prescription for treating retinal diseases for years. Our preliminary experiment showed that mZJP exerted an antioxidant effect in treating dry age-related macular degeneration (AMD). Nevertheless, the specific mechanism underpinning the impact of mZJP on dry AMD remains obscure.
Methods: The chemical metabolites of mZJP were qualitatively analyzed using LC-Q-TOF-MS. Dry AMD model mice were used to assess the efficacy of mZJP through optical coherence tomography (OCT), fundus autofluorescence (FAF), and immunofluorescence. Epithelial-mesenchymal transition (EMT) in OxLDL-induced ARPE-19 cells was evaluated by monitoring cellular integrity and quantifying EMT-related markers. Cell migration capacity was determined via wound healing and transwell assays. To investigate molecular mechanisms, cells were transfected with Nrf2 siRNA and analyzed through Western blotting, immunofluorescence, and migration assays under Nrf2 inhibition.
Results: A total of 113 major metabolites were identified in mZJP. Our findings revealed that mZJP alleviated retinal pathological alterations and inhibited EMT progression. Furthermore, mZJP upregulated Nrf2 and HO-1 expression levels while downregulating Akt and GSK-3β phosphorylation levels. Notably, the EMT-suppressing effect of mZJP was significantly attenuated upon Nrf2 silencing, as evidenced by enhanced cell migration, decreased epithelial marker expression (E-cadherin), increased mesenchymal marker expression (vimentin and α-SMA), suppression of the Nrf2 pathway, and activation of the Akt/GSK3β pathway.
Conclusion: Our study suggested that RPE protection by mZJP against oxidative stress induced EMT through Nrf2 activation and inhibition of the Akt/GSK3β pathway. MZJP could be a potential candidate drug for the treatment of dry AMD.

Keywords: Akt/GSK3β pathway; Nrf2 pathway; age-related macular degeneration; epithelial–mesenchymal transition; modified ZhuJing pill

DOI: https://doi.org/10.3389/fphar.2025.1545731

Aging Cell. 2025 Jun 20. e70150

Naphthalene Metabolites From Long-Term Environmental Tobacco Smoke Induce the Aging of Retinal Pigment Epithelium.

Tingting Cui, Qingjian Ou, Zhe Wang, Ye Zhou, Jinyuan Xu, Yifan Liu, Yanlong Bi, Xiaoliang Jin, Jie Chen, Furong Gao, Juan Wang, Jieping Zhang, Lixia Lu, Guo-Tong Xu, Caixia Jin, Haibin Tian, Jing-Ying Xu.

Tobacco use is the main source of indoor air pollution and contains a variety of toxic components. The smoke from burning cigarettes is a key environmental risk factor that leads to accelerated aging and the occurrence of numerous diseases. Meanwhile, cigarette smoke and aging are both prominent risk factors for age-related macular degeneration (AMD). This study demonstrates that long-term exposure to cigarette smoke can impair retinal function and induce the aging of retinal pigment epithelium (RPE). Meanwhile, the plasma of rats after long-term exposure to cigarette smoke can trigger DNA damage and cellular senescence in vitro. In addition, naphthalene and its metabolites (1,2-dihydroxynaphthalene and 1,2-naphthoquinone) derived from cigarette smoke have been identified as an important factor contributing to RPE damage caused by cigarette exposure. Finally, we found that the aging of RPE induced by smoking can be alleviated through smoking cessation, probably because quitting smoking reduces the accumulation of these toxic chemicals in plasma and within the eyes.

Keywords: 1,2‐Dihydroxynaphthalene; 1,2‐Naphthoquinone; RPE senescence; cigarette exposure; environmental tobacco smoke; smoking cessation

DOI: https://doi.org/10.1111/acel.70150

Front Ophthalmol (Lausanne). 2025 ;5 1610215

Exploiting induced pluripotent stem cell-derived retinal pigment epithelium to unravel host-pathogen interaction in ocular tuberculosis: a reverse translational in vitro model.

Ikhwanuliman Putera, Sanne van de Meerendonk, Nicole M A Nagtzaam, Rina La Distia Nora, Saskia M Rombach, Jurriaan E M de Steenwinkel, Johannes R Vingerling, Willem A Dik, P Martin van Hagen.

Mycobacterium tuberculosis (Mtb) can infect the retinal pigment epithelium (RPE) cells. Current in vitro research models for ocular tuberculosis (OTB) only rely on RPE cell culture approaches. Until now it remains unclear why only a minority of patients with active systemic tuberculosis (TB) develops concurrent OTB. There is significant variation in the clinical manifestations of OTB, which is potentially influenced by ethnic differences and diversity in mycobacterial strains. To better understand the immunopathobiology of OTB, particularly an individual's susceptibility to Mtb-infection and the specific host response, cell culture systems utilizing induced pluripotent stem cells (iPSC)-derived RPE cells offer a promising in vitro model to better mimic the disease. With this technology, RPE cells can be generated from specific patients of interest, enabling to test hypotheses in a bench to bedside or reverse manner. In this current study, we explore the utility of iPSC-derived RPE cells as an in vitro model for OTB. Such an approach would overcome drawbacks associated with the currently commonly used "general" RPE cell lines as disease model. The application of iPSC-derived RPE cells offers promising options for the identification of novel biomarkers and to study individualized drug screening methods for host-directed therapy of OTB, in order to restore and maintain vision in OTB patients with sight-threatening disease.

Keywords: induced pluripotent stem cells; personalized medicine; retinal pigment epithelium; tuberculosis; uveitis

DOI: https://doi.org/10.3389/fopht.2025.1610215