International Journal of Molecular Sciences

Editorial

5 pages, 184 KiB

Open AccessEditorial

Special Issue “The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies”

by Snježana Kaštelan

Int. J. Mol. Sci. 2024, 25(4), 2405; https://doi.org/10.3390/ijms25042405 - 18 Feb 2024

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Abstract

Visual impairment and ophthalmic diseases represent significant global public health concerns, and their prevalence continues to rise [...] Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

Research

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15 pages, 5796 KiB

Open AccessArticle

The Human Ocular Surface Microbiome and Its Associations with the Tear Proteome in Dry Eye Disease

by Irina Schlegel, Claire M. F. De Goüyon Matignon de Pontourade, Joel-Benjamin Lincke, Irene Keller, Martin S. Zinkernagel and Denise C. Zysset-Burri

Int. J. Mol. Sci. 2023, 24(18), 14091; https://doi.org/10.3390/ijms241814091 - 14 Sep 2023

Cited by 2 | Viewed by 1722

Abstract

Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially [...] Read more.

Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially leading to inflammatory processes, are associated with ocular surface diseases such as DED. In this study, we aimed to find unique compositional and functional features of the OSM associated with human and microbial tear proteins in patients with DED. Applying whole-metagenome shotgun sequencing of forty lid and conjunctival swabs, we identified 229 taxa, with Actinobacteria and Proteobacteria being the most abundant phyla and Propionibacterium acnes the dominating species in the cohort. When DED patients were compared to controls, the species Corynebacterium tuberculostearicum was more abundant in conjunctival samples, whereas the family Propionibacteriaceae was more abundant in lid samples. Functional analysis showed that genes of L-lysine biosynthesis, tetrapyrrole biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis, and the super pathway of L-threonine biosynthesis were enriched in conjunctival samples of controls. The relative abundances of Acinetobacter johnsonii correlated with seven human tear proteins, including mucin-16. The three most abundant microbial tear proteins were the chaperone protein DnaK, the arsenical resistance protein ArsH, and helicase. Compositional and functional features of the OSM and the tear proteome are altered in patients with DED. Ultimately, this may help to design novel interventional therapeutics to target DED. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

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14 pages, 4524 KiB

Open AccessArticle

Expression of Androgen and Estrogen Receptors in the Human Lacrimal Gland

by Koraljka Hat, Ana Planinić, Davor Ježek and Snježana Kaštelan

Int. J. Mol. Sci. 2023, 24(6), 5609; https://doi.org/10.3390/ijms24065609 - 15 Mar 2023

Cited by 6 | Viewed by 1413

Abstract

Lacrimal gland dysfunction causes dry eye disease (DED) due to decreased tear production. Aqueous-deficient DED is more prevalent in women, suggesting that sexual dimorphism of the human lacrimal gland could be a potential cause. Sex steroid hormones are a key factor in the [...] Read more.

Lacrimal gland dysfunction causes dry eye disease (DED) due to decreased tear production. Aqueous-deficient DED is more prevalent in women, suggesting that sexual dimorphism of the human lacrimal gland could be a potential cause. Sex steroid hormones are a key factor in the development of sexual dimorphism. This study aimed to quantify estrogen receptor (ER) and androgen receptor (AR) expression in the human lacrimal gland and compare it between sexes. RNA was isolated from 35 human lacrimal gland tissue samples collected from 19 cornea donors. AR, ERα, and ERβ mRNA was identified in all samples, and their expression was quantified using qPCR. Immunohistochemical staining was performed on selected samples to evaluate protein expression of the receptors. ERα mRNA expression was significantly higher than the expression of AR and ERβ. No difference in sex steroid hormone (SSH) receptor mRNA expression was observed between sexes, and no correlation was observed with age. If ERα protein expression is found to be concordant with mRNA expression, it should be investigated further as a potential target for hormone therapy of DED. Further research is needed to elucidate the role of sex steroid hormone receptors in sex-related differences of lacrimal gland structure and disease. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

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Review

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19 pages, 1311 KiB

Open AccessReview

Tear Biomarkers and Alzheimer’s Disease

by Snježana Kaštelan, Marijana Braš, Neda Pjevač, Ivana Bakija, Zora Tomić, Nada Pjevač Keleminić and Antonela Gverović Antunica

Int. J. Mol. Sci. 2023, 24(17), 13429; https://doi.org/10.3390/ijms241713429 - 30 Aug 2023

Cited by 1 | Viewed by 1894

Abstract

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative brain disorder that represents the most common type of dementia. It poses a significant diagnostic challenge that requires timely recognition and treatment. Currently, there is no effective therapy for AD; however, certain medications may slow [...] Read more.

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative brain disorder that represents the most common type of dementia. It poses a significant diagnostic challenge that requires timely recognition and treatment. Currently, there is no effective therapy for AD; however, certain medications may slow down its progression. The discovery of AD biomarkers, namely, magnetic resonance imaging, positron emission tomography and cerebrospinal fluid molecules (amyloid-β and tau) has advanced our understanding of this disease and has been crucial for identifying early neuropathologic changes prior to clinical changes and cognitive decline. The close interrelationship between the eye and the brain suggests that tears could be an interesting source of biomarkers for AD; however, studies in this area are limited. The identification of biomarkers in tears will enable the development of cost-effective, non-invasive methods of screening, diagnosis and disease monitoring. In order to use tears as a standard method for early and non-invasive diagnosis of AD, future studies need to be conducted on a larger scale. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

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22 pages, 971 KiB

Open AccessReview

Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications

by Daria Pašalić, Tamara Nikuševa-Martić, Ankica Sekovanić and Snježana Kaštelan

Int. J. Mol. Sci. 2023, 24(16), 12807; https://doi.org/10.3390/ijms241612807 - 15 Aug 2023

Cited by 2 | Viewed by 1118

Abstract

Uveal melanoma (UM) is rare, but it is the most common primary intraocular malignancy among adults. This review represents the molecular, genetic, and immunobiological mechanisms involved in UM carcinogenesis and progression, as well as data about the association of chromosomal changes, genetic mutations, [...] Read more.

Uveal melanoma (UM) is rare, but it is the most common primary intraocular malignancy among adults. This review represents the molecular, genetic, and immunobiological mechanisms involved in UM carcinogenesis and progression, as well as data about the association of chromosomal changes, genetic mutations, selective proteins, and biochemical biomarkers with the clinical implications of UM. Genetic analysis has the potential to identify patients with a high risk of UM metastasis, enabling management that is more effective and allowing for the follow-up of patients. Advancements in molecular characterization of UM offer opportunities to develop targeted therapeutic strategies by focusing on relevant signaling pathways. Changes in miRNA expression could be useful in the diagnosis and prognosis of UM, due to unique miRNA profiles in melanoma cells or tissue and its association with metastasis. Although liver function tests do not provide enough data on the prognosis of UM, due to the high frequency of liver metastasis, liver function tests (LFTs) might be useful indicators; however, the absence of rising LFT values cannot lead to the exclusion of liver metastases. Molecular analysis of tumor tissue will allow us to identify patients with the added benefit of new therapeutic agents and provide a better insight into melanoma pathogenesis and its biological behavior. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

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10 pages, 276 KiB

Open AccessReview

Vitamin D and Diabetic Retinopathy

by Antonela Gverović Antunica, Ljubo Znaor, Mira Ivanković, Velibor Puzović, Irena Marković and Snježana Kaštelan

Int. J. Mol. Sci. 2023, 24(15), 12014; https://doi.org/10.3390/ijms241512014 - 27 Jul 2023

Cited by 2 | Viewed by 1495

Abstract

Diabetic retinopathy (DR) is the most common eye disease complication of diabetes, and hypovitaminosis D is mentioned as one of the risk factors. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are the best-known forms of vitamin D. Calcitriol (1,25-dihydroxycholecalciferol) is the active form [...] Read more.

Diabetic retinopathy (DR) is the most common eye disease complication of diabetes, and hypovitaminosis D is mentioned as one of the risk factors. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are the best-known forms of vitamin D. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, with the sun being one of its main sources. Vitamin D is synthesized in the skin by exposure to sunlight without protective factors, but care must be taken to avoid the development of sunburn. It not only plays an important role in maintaining healthy bones and immune system but has also been highlighted in numerous studies to have an influence on various diseases, including diabetic retinopathy. A large number of people suffer from vitamin D hypovitaminosis worldwide, and diagnosis is made by measuring the concentration of 25-hydroxyvitamin D (25(OH)D) in serum. Its deficiency can cause numerous diseases and, as such, supplementation is necessary. Clinical studies have proven the effectiveness of vitamin D supplementation in the treatment of diabetic retinopathy, but with a doctor’s recommendation and supervision due to possible negative side effects. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

19 pages, 1182 KiB

Open AccessReview

A Mediterranean Diet May Be Protective in the Development of Diabetic Retinopathy

by Anna Bryl, Małgorzata Mrugacz, Mariusz Falkowski and Katarzyna Zorena

Int. J. Mol. Sci. 2023, 24(13), 11145; https://doi.org/10.3390/ijms241311145 - 06 Jul 2023

Cited by 2 | Viewed by 2227

Abstract

The Mediterranean diet is recognized as one of the healthiest available dietary patterns. This perception results from its beneficial effects on the cardiovascular system and, also, on hypertension, diabetes, and cancer compared with other diets. Its impact on the course of diabetes is [...] Read more.

The Mediterranean diet is recognized as one of the healthiest available dietary patterns. This perception results from its beneficial effects on the cardiovascular system and, also, on hypertension, diabetes, and cancer compared with other diets. Its impact on the course of diabetes is assessed in the available scientific literature; however, little information is available about its impact on diabetic retinopathy. The MD is characterized mainly by the consumption of fish, seafood, foods of plant origin, and fresh fruit and vegetables. It is also recommended to consume legumes, which are a source of folic acid, magnesium, iron, and dietary fiber. High consumption of nuts and unrefined grains is also recommended in the MD. Marine fish provide polyunsaturated acids from the omega-3 group. Olive oil plays a very important role, especially olive oil obtained from mechanical pressing. Additionally, olive oil contains vitamins E, K, and polyphenols. Polyphenols, which are present in a diverse range of vegetables, fruits, and seeds, have the ability to decrease oxidative stress, inflammation, and insulin resistance. Resveratrol is naturally found in grape skins and seeds, as well as in peanuts and berries, and is a constituent of red wine. Resveratrol can inhibit increased vascular leakage and loss of pericytes and regulate the level of VEGF protein in the retina, thus inhibiting the development of DR. Consumption of fruits, vegetables, fish, and olive oil may be correlated with a lower risk of diabetic retinopathy. This paper presents the definition of the Mediterranean diet and its influence on the course of diabetes and diabetic retinopathy. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

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22 pages, 1186 KiB

Open AccessReview

Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases

by Maddalen Zufiaurre-Seijo, José García-Arumí and Anna Duarri

Int. J. Mol. Sci. 2023, 24(13), 10670; https://doi.org/10.3390/ijms241310670 - 26 Jun 2023

Cited by 3 | Viewed by 1692

Abstract

Mutations in the photoreceptor-specific C2orf71 gene (also known as photoreceptor cilium actin regulator protein PCARE) cause autosomal recessive retinitis pigmentosa type 54 and cone-rod dystrophy. No treatments are available for patients with C2orf71 retinal ciliopathies exhibiting a severe clinical phenotype. Our understanding of [...] Read more.

Mutations in the photoreceptor-specific C2orf71 gene (also known as photoreceptor cilium actin regulator protein PCARE) cause autosomal recessive retinitis pigmentosa type 54 and cone-rod dystrophy. No treatments are available for patients with C2orf71 retinal ciliopathies exhibiting a severe clinical phenotype. Our understanding of the disease process and the role of PCARE in the healthy retina significantly limits our capacity to transfer recent technical developments into viable therapy choices. This study summarizes the current understanding of C2orf71-related retinal diseases, including their clinical manifestations and an unclear genotype-phenotype correlation. It discusses molecular and functional studies on the photoreceptor-specific ciliary PCARE, focusing on the photoreceptor cell and its ciliary axoneme. It is proposed that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane during the development of a new outer segment disk in photoreceptor cells. This review also introduces various cellular and animal models used to model these diseases and provides an overview of potential treatments. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

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Other

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9 pages, 11044 KiB

Open AccessCase Report

Rituximab, Intravitreal Bevacizumab and Laser Photocoagulation for Treatment of Macrophage Activation Syndrome and Retinal Vasculitis in Lupus: A Case Report

by Marina Ikić Matijašević, Paula Kilić, Lucija Ikić, Iva Galić, Vlatka Brzović Šarić and Edvard Galić

Int. J. Mol. Sci. 2023, 24(3), 2594; https://doi.org/10.3390/ijms24032594 - 30 Jan 2023

Cited by 4 | Viewed by 1558

Abstract

Systemic lupus erythematosus (SLE) most commonly manifests as mild to moderate disease with severe manifestations such as diffuse alveolar hemorrhage, central nervous system vasculitis, macrophage activation syndrome (MAS) or retinal vasculitis (RV) with visual disturbances occurring in a significantly smaller proportion of patients, [...] Read more.

Systemic lupus erythematosus (SLE) most commonly manifests as mild to moderate disease with severe manifestations such as diffuse alveolar hemorrhage, central nervous system vasculitis, macrophage activation syndrome (MAS) or retinal vasculitis (RV) with visual disturbances occurring in a significantly smaller proportion of patients, most of whom have a poor outcome. Macrophage activation syndrome and RV are insufficiently early and rarely recognized presentations of lupus—consequently there are still no treatment recommendations. Here we present the course of diagnosis and treatment of a patient with an SLE flare that resulted in both life-threatening disease (MAS) and vision-threatening disease (RV). The patient was successfully treated with systemic immunosuppressives, a high dose of glucocorticoids and rituximab (RTX), in parallel with intraocular therapy, intravitreal bevacizumab (BEV) and laser photocoagulation. Full article

(This article belongs to the Special Issue The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies)

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