International Journal of Molecular Sciences

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Dear Colleagues,

The relationship between ocular alterations and systemic diseases has recently gained significant attention. The eye offers a unique opportunity for the direct, in vivo observation of the neurosensory and microvascular systems. Numerous systemic diseases have ocular manifestations such as diabetes mellitus, neurodegenerative, psychiatric, cardiovascular, endocrinological, haematological, nutritional, respiratory, autoimmune, and systemic inflammatory diseases and malignancies. Additionally, pregnancy, various genetic syndromes, as well as certain medications and medical treatments may potentially induce ocular changes. In some cases, the ocular findings may be the initial manifestation of the systemic disease preceding the appearance of systemic symptoms. Given the significance of ocular changes as potential biomarkers for systemic diseases, it is essential for medical specialists and interdisciplinary researchers to comprehend the interrelationships between ocular findings and systemic diseases and conditions. This understanding is crucial for translating the acquired knowledge into improved diagnostic and therapeutic algorithms, both at the individual and population levels.

This Special Issue encompasses research that provides new insights into cellular and molecular mechanisms, focusing on the latest advancements in understanding ocular pathology and its associations with various systemic conditions. The objective of this Special Issue is to present new advancements and discoveries in this field. Therefore, all manuscripts, including case reports, commentaries, short communications, clinical reports, experimental research and reviews, as well as meta-analyses, reporting associations between eye disease and changes linked to different systemic conditions, are welcome. Data on molecular mechanisms or pathophysiology are essential, and papers that only contain clinical trials/data are not acceptable.

Dr. Snježana Kaštelan
Prof. Dr. Katarzyna Zorena
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

ocular pathology
systemic disorders
biomarkers
pathogenetic mechanism
cellular and molecular mechanisms
diagnostic techniques
imaging technologies
treatment

Published Papers (2 papers)

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Research

22 pages, 3709 KiB

Open AccessArticle

Thermosensitive TRP Channels Are Functionally Expressed and Influence the Lipogenesis in Human Meibomian Gland Cells

by Melina Keller, Stefan Mergler, Aruna Li, Ingrid Zahn, Friedrich Paulsen and Fabian Garreis

Int. J. Mol. Sci. 2024, 25(7), 4043; https://doi.org/10.3390/ijms25074043 - 05 Apr 2024

Viewed by 610

Abstract

While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the meibomian gland (MG) has never been investigated. This study aims to show their expression and involvement in the lipogenesis of the MG, providing a possible new drug target in the treatment of DED. Our RT-PCR, Western blot and immunofluorescence analysis showed the expression of TRPV1, TRPV3, TRPV4 and TRPM8 in the MG at the gene and the protein level. RT-PCR also showed gene expression of TRPV2 but not TRPA1. Calcium imaging and planar patch-clamping performed on an immortalized human meibomian gland epithelial cell line (hMGECs) demonstrated increasing whole-cell currents after the application of capsaicin (TRPV1) or icilin (TRPM8). Decreasing whole-cell currents could be registered after the application of AMG9810 (TRPV1) or AMTB (TRPM8). Oil red O staining on hMGECs showed an increase in lipid expression after TRPV1 activation and a decrease after TRPM8 activation. We conclude that thermo-TRPs are expressed at the gene and the protein level in MGs. Moreover, TRPV1 and TRPM8’s functional expression and their contribution to their lipid expression could be demonstrated. Therefore, TRPs are potential drug targets and their clinical relevance in the therapy of meibomian gland dysfunction requires further investigation. Full article

(This article belongs to the Special Issue Cellular and Molecular Insights into Ocular Changes Associated with Systemic Disorders and Conditions)

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19 pages, 5015 KiB

Open AccessArticle

Cholesterol Content Regulates the Interaction of αA-, αB-, and α-Crystallin with the Model of Human Lens-Lipid Membranes

by Raju Timsina, Preston Hazen, Geraline Trossi-Torres, Nawal K. Khadka, Navdeep Kalkat and Laxman Mainali

Int. J. Mol. Sci. 2024, 25(3), 1923; https://doi.org/10.3390/ijms25031923 - 05 Feb 2024

Viewed by 674

Abstract

α-Crystallin (αABc) is a major protein comprised of αA-crystallin (αAc) and αB-crystallin (αBc) that is found in the human eye lens and works as a molecular chaperone by preventing the aggregation of proteins and providing tolerance to stress. However, with age and cataract formation, the concentration of αABc in the eye lens cytoplasm decreases, with a corresponding increase in the membrane-bound αABc. This study uses the electron paramagnetic resonance (EPR) spin-labeling method to investigate the role of cholesterol (Chol) and Chol bilayer domains (CBDs) in the binding of αAc, αBc, and αABc to the Chol/model of human lens-lipid (Chol/MHLL) membranes. The maximum percentage of membrane surface occupied (MMSO) by αAc, αBc, and αABc to Chol/MHLL membranes at a mixing ratio of 0 followed the trends: MMSO (αAc) > MMSO (αBc) ≈ MMSO (αABc), indicating that a higher amount of αAc binds to these membranes compared to αBc and αABc. However, with an increase in the Chol concentration in the Chol/MHLL membranes, the MMSO by αAc, αBc, and αABc decreases until it is completely diminished at a mixing ratio of 1.5. The K_a of αAc, αBc, and αABc to Chol/MHLL membranes at a mixing ratio of 0 followed the trend: K_a (αBc) ≈ K_a (αABc) > K_a (αAc), but it was close to zero with the diminished binding at a Chol/MHLL mixing ratio of 1.5. The mobility near the membrane headgroup regions decreased with αAc, αBc, and αABc binding, and the Chol antagonized the capacity of the αAc, αBc, and αABc to decrease mobility near the headgroup regions. No significant change in membrane order near the headgroup regions was observed, with an increase in αAc, αBc, and αABc concentrations. Our results show that αAc, αBc, and αABc bind differently with Chol/MHLL membranes at mixing ratios of 0 and 0.5, decreasing the mobility and increasing hydrophobicity near the membrane headgroup region, likely forming the hydrophobic barrier for the passage of polar and ionic molecules, including antioxidants (glutathione), creating an oxidative environment inside the lens, leading to the development of cataracts. However, all binding was completely diminished at a mixing ratio of 1.5, indicating that high Chol and CBDs inhibit the binding of αAc, αBc, and αABc to membranes, preventing the formation of hydrophobic barriers and likely protecting against cataract formation. Full article

(This article belongs to the Special Issue Cellular and Molecular Insights into Ocular Changes Associated with Systemic Disorders and Conditions)

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