International Journal of Molecular Sciences

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Eye Diseases: From Pathophysiology to Novel Therapeutic Approaches

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Dear Colleagues,

The progress made in clinical and experimental ophthalmology in recent years is remarkable. It would not be possible without developments in our progressively better understanding of the pathophysiology of eye diseases. New medicines and therapeutic strategies which have been introduced and implemented into everyday clinical practice are consequences of the work of laboratory experiments and observations on genetic, biochemical, proteomic, cellular, and physiological levels. In this Special Issue, entitled "Eye Diseases: From Pathophysiology to Novel Therapeutic Approaches", we welcome authors to submit papers that highlight new achievements in these fields. We encourage submissions focused on the molecular mechanisms underlying eye diseases and innovative therapeutic approaches, rooted in molecular research. We hope that improving our knowledge and outlining the most recent achievements in molecular insights brings new therapeutic possibilities to help rescue vision and inspires our readers and scientists by the new discoveries in both experimental and clinical ophthalmology.

Dr. Tomasz Chorągiewicz
Dr. Joanna Dolar-Szczasny
Guest Editors

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21 pages, 1040 KiB

Open AccessReview

Changes in the Protein Composition of the Aqueous Humor in Patients with Glaucoma: An Update Review

by Maria Kiełbus, Dominika Kuźmiuk, Aleksandra Magdalena Skrzyniarz, Aleksandra Zynkowska, Joanna Dolar-Szczasny, Tomasz Chorągiewicz and Robert Rejdak

Int. J. Mol. Sci. 2025, 26(7), 3129; https://doi.org/10.3390/ijms26073129 - 28 Mar 2025

Viewed by 638

Abstract

The study of the aqueous humor (AH) plays a key role in understanding the pathophysiology of glaucoma. The AH provides nutrition, maintains the appropriate intraocular pressure, and provides important information about the mechanisms of the disease. The development of modern technologies has allowed the use of more accurate analytical methods, which has proven to be a key factor in determining the changes occurring in the proteome of the aqueous humor of glaucoma patients. Recently, researchers have observed changes in the levels of proteins associated with inflammation, oxidative stress, the complement system, and extracellular matrix remodeling. They have also shown that these changes may be variable for different types of glaucoma. The objective of this review is to collect and summarize the current knowledge on the potential biomarkers and pathomechanisms involved in the pathogenesis of glaucoma. We hope that our review will contribute to the improvement of current diagnostic methods in this illness and, through a better understanding of the changes occurring during the progression of the disease, will enable the development of more effective preventive and therapeutic strategies in the future. Full article

(This article belongs to the Special Issue Eye Diseases: From Pathophysiology to Novel Therapeutic Approaches)

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22 pages, 2570 KiB

Open AccessArticle

Tacrolimus Modulates TGF-β Signaling–Related Genes and MicroRNAs in Human Retinal Pigment Epithelial Cells Activated by Lipopolysaccharide

by Aleksandra Kiełbasińska, Katarzyna Krysik, Dominika Janiszewska-Bil, Martyna Machaj, Zuzanna Lelek, Joanna Sułkowska, Olga Nawotny-Czupryna and Beniamin Oskar Grabarek

Int. J. Mol. Sci. 2025, 26(11), 5402; https://doi.org/10.3390/ijms26115402 - 4 Jun 2025

Viewed by 108

Abstract

The retinal pigment epithelium (RPE) plays a crucial role in maintaining retinal homeostasis, and dysregulation of the transforming growth factor-beta (TGF-β) signaling pathways contributes to retinal fibrosis and inflammatory diseases, including proliferative vitreoretinopathy (PVR). Tacrolimus (FK506), an immunosuppressant, has shown potential antifibrotic properties, but its effects on TGF-β-related genes and microRNAs (miRNAs) in RPE cells remain unclear. Human RPE (H-RPE) cells were treated with lipopolysaccharide (LPS) to induce inflammation and subsequently exposed to tacrolimus. Gene and miRNA expression profiling related to TGF-β signaling pathways were conducted using microarrays, followed by Quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR) validation. Protein levels were assessed via enzyme-linked immunosorbent assay (ELISA), and interactions were analyzed using STRING database network analysis. Tacrolimus modulated key components of the TGF-β pathway, upregulating TGF-β2, TGF-β3, SMAD2, and SMAD4 while downregulating TGF-βR1 and SMAD7. JAK/STAT and MAPK pathways were also affected, indicating broad regulatory effects. miRNA profiling identified hsa-miR-200a-3p, hsa-miR-589-3p, hsa-miR-21, and hsa-miR-27a-5p as key regulators. STRING analysis confirmed strong functional interactions within the TGF-β network. In conclusion, tacrolimus modulates both canonical (upregulation of SMAD2/4 and downregulation of SMAD7) and non-canonical (JAK/STAT and MAPK) TGF-β signaling pathways in LPS-stimulated RPE cells. These changes collectively suggest a dual anti-inflammatory and anti-fibrotic effect. The increased TGF-β2 and decreased SMAD7 levels, alongside altered miRNA expression (e.g., downregulation of miR-200a-3p), indicate that tacrolimus may inhibit key profibrotic mechanisms underlying PVR. These findings support the potential therapeutic repurposing of tacrolimus in PVR and warrant further in vivo validation. Full article

(This article belongs to the Special Issue Eye Diseases: From Pathophysiology to Novel Therapeutic Approaches)

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