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1.
Front Pharmacol ; 15: 1375805, 2024.
Article En | MEDLINE | ID: mdl-38590636

Introduction: The purine analog 6-thioguanine (6TG), an old drug approved in the 60s to treat acute myeloid leukemia (AML), was tested in the diabetic retinopathy (DR) experimental in vivo setting along with a molecular modeling approach. Methods: A computational analysis was performed to investigate the interaction of 6TG with MC1R and MC5R. This was confirmed in human umbilical vein endothelial cells (HUVECs) exposed to high glucose (25 mM) for 24 h. Cell viability in HUVECs exposed to high glucose and treated with 6TG (0.05-0.5-5 µM) was performed. To assess tube formation, HUVECs were treated for 24 h with 6TG 5 µM and AGRP (0.5-1-5 µM) or PG20N (0.5-1-5-10 µM), which are MC1R and MC5R antagonists, respectively. For the in vivo DR setting, diabetes was induced in C57BL/6J mice through a single streptozotocin (STZ) injection. After 2, 6, and 10 weeks, diabetic and control mice received 6TG intravitreally (0.5-1-2.5 mg/kg) alone or in combination with AGRP or PG20N. Fluorescein angiography (FA) was performed after 4 and 14 weeks after the onset of diabetes. After 14 weeks, mice were euthanized, and immunohistochemical analysis was performed to assess retinal levels of CD34, a marker of endothelial progenitor cell formation during neo-angiogenesis. Results: The computational analysis evidenced a more stable binding of 6TG binding at MC5R than MC1R. This was confirmed by the tube formation assay in HUVECs exposed to high glucose. Indeed, the anti-angiogenic activity of 6TG was eradicated by a higher dose of the MC5R antagonist PG20N (10 µM) compared to the MC1R antagonist AGRP (5 µM). The retinal anti-angiogenic effect of 6TG was evident also in diabetic mice, showing a reduction in retinal vascular alterations by FA analysis. This effect was not observed in diabetic mice receiving 6TG in combination with AGRP or PG20N. Accordingly, retinal CD34 staining was reduced in diabetic mice treated with 6TG. Conversely, it was not decreased in diabetic mice receiving 6TG combined with AGRP or PG20N. Conclusion: 6TG evidenced a marked anti-angiogenic activity in HUVECs exposed to high glucose and in mice with DR. This seems to be mediated by MC1R and MC5R retinal receptors.

2.
Microorganisms ; 12(4)2024 Apr 09.
Article En | MEDLINE | ID: mdl-38674702

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening corneal infection caused by the Acanthamoeba parasite. This microorganism is found ubiquitously in the environment, often in freshwater, soil, and other sources of moisture. Despite its low incidence, AK presents significant challenges due to delayed diagnosis and the complex nature of therapeutic management. Early recognition is crucial to prevent severe ocular complications, including corneal ulceration and vision loss. Diagnostic modalities and treatment strategies may vary greatly depending on the clinical manifestation and the available tools. With the growing reported cases of Acanthamoeba keratitis, it is essential for the ophthalmic community to thoroughly understand this condition for its effective management and improved outcomes. This review provides a comprehensive overview of AK, encompassing its epidemiology, risk factors, pathophysiology, clinical manifestations, diagnosis, and treatment.

3.
J Orthop Traumatol ; 25(1): 11, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38418743

BACKGROUND: Proximal humeral fractures (PHFs) are still controversial with regards to treatment and are difficult to classify. The study's objective is to show that preoperative planning performed while handling a three-dimensional (3D) printed anatomical model of the fracture can ensure a better understanding of trauma for both surgeons and patients. MATERIALS AND METHODS: Twenty patients (group A, cases) with complex PHF were evaluated preoperatively by reproducing life-size, full-touch 3D anatomical models. Intraoperative blood loss, radiographic controls, duration of surgery, and clinical outcomes of patients in group A were compared with 20 patients (group B, controls) who underwent standard preoperative evaluation. Additionally, senior surgeons and residents, as well as group A patients, answered a questionnaire to evaluate innovative preoperative planning and patient compliance. Cost analysis was evaluated. RESULTS: Intraoperative radiography controls and length of operation were significantly shorter in group A. There were no differences in clinical outcomes or blood loss. Patients claim a better understanding of the trauma suffered and the proposed treatment. Surgeons assert that the planning of the definitive operation with 3D models has had a good impact. The development of this tool has been well received by the residents. The surgery was reduced in length by 15%, resulting in savings of about EUR 400 for each intervention. CONCLUSIONS: Fewer intraoperative radiography checks, shorter surgeries, and better patient compliance reduce radiation exposure for patients and healthcare staff, enhance surgical outcomes while reducing expenses, and lower the risk of medicolegal claims. LEVEL OF EVIDENCE: Level I, prospective randomized case-control study.


Patient Satisfaction , Shoulder Fractures , Humans , Case-Control Studies , Operative Time , Prospective Studies , Shoulder Fractures/diagnostic imaging , Shoulder Fractures/surgery , Fracture Fixation, Internal/methods , Costs and Cost Analysis
4.
Medicina (Kaunas) ; 60(1)2024 Jan 08.
Article En | MEDLINE | ID: mdl-38256379

Background and Objectives: The role and the levels of ghrelin in diabetes-induced retinal damage have not yet been explored. The present study aimed to measure the serum levels of total ghrelin (TG), and its acylated (AG) and des-acylated (DAG) forms in patients with the two stages of diabetic retinopathy (DR), non-proliferative (NPDR) and proliferative (PDR). Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels was investigated. Materials and Methods: The serum markers were determined via enzyme-linked immunosorbent assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with NPDR, and 15 patients with PDR. Results: TG and AG serum levels were significantly decreased in Diabetic (respectively, p < 0.05 and p < 0.01 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and in PDR patients (p < 0.01 vs. NPDR). AG serum levels were inversely associated with DR abnormalities (microhemorrhages, microaneurysms, and exudates) progression (r = -0.83, p < 0.01), serum neutrophil percentage (r = -0.74, p < 0.01), and serum NE levels (r = -0.73, p < 0.01). The latter were significantly increased in the Diabetic (p < 0.05 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and PDR (p < 0.01 vs. PDR) groups. Conclusions: The two DR stages were characterized by decreased AG and increased NE levels. In particular, serum AG levels were lower in PDR compared to NPDR patients, and serum NE levels were higher in the PDR vs. the NPDR group. Together with the greater presence of retinal abnormalities, this could underline a distinctive role of AG in PDR compared to NPDR.


Diabetes Mellitus , Diabetic Retinopathy , Humans , Leukocyte Elastase , Ghrelin , Enzyme-Linked Immunosorbent Assay , Exudates and Transudates
5.
Pharmaceutics ; 15(10)2023 Oct 13.
Article En | MEDLINE | ID: mdl-37896220

Diabetic macular edema (DME)'s therapeutic approach can frequently be challenging. The purpose of the review is to propose evidence-based recommendations on the employment of intravitreal dexamethasone implants (DEX) when approaching patients suffering from DME. Seven national consensuses redacted by different groups of retina specialists from Europe and Asia were examined and confronted. Each consensus was redacted utilizing a Delphi approach, in person meetings, or by reviewing the literature. DEX can be studied as a first-line strategy in individuals suffering from DME with inflammatory OCT biomarkers, in vitrectomized eyes, in patients with recent cardiovascular events, in pregnant women, in patients scheduled to undergo cataract surgery or with poor compliance. The other parameters considered were the indications to the DME treatment, when to switch to DEX, the definition of non-responder to anti-VEGFs agents and to the DEX implant, whether to combine DEX with laser photocoagulation, the association between glaucoma and DEX, and the management of DEX and the cataract. Although several years have passed since the introduction of DEX implants in the DME treatment, there is still not a unified agreement among retina specialists. This paper compares the approach in the DME treatment between countries from different continents and provides a broader and worldwide perspective of the topic.

6.
Antibiotics (Basel) ; 12(8)2023 Aug 02.
Article En | MEDLINE | ID: mdl-37627697

Fungi represent a very important cause of microbial eye infections, especially in tropical and developing countries, as they could cause sight-threating disease, such as keratitis and ocular candidiasis, resulting in irreversible vision loss. Candida species are among the most frequent microorganisms associated with fungal infection. Although Candida albicans is still the most frequently detected organism among Candida subspecies, an important increase in non-albicans species has been reported. Mycotic infections often represent an important diagnostic-clinical problem due to the difficulties in performing the diagnosis and a therapeutic problem due to the limited availability of commercial drugs and the difficult penetration of antifungals into ocular tissues. The ability to form biofilms is another feature that makes Candida a dangerous pathogen. In this review, a summary of the state-of-the-art panorama about candida ocular pathology, diagnosis, and treatment has been conducted. Moreover, we also focused on new prospective natural compounds, including nanoparticles, micelles, and nanocarriers, as promising drug delivery systems to better cure ocular fungal and biofilm-related infections. The effect of the drug combination has also been examined from the perspective of increasing efficacy and improving the course of infections caused by Candida which are difficult to fight.

7.
Int J Mol Sci ; 24(16)2023 Aug 17.
Article En | MEDLINE | ID: mdl-37629056

The fungal species Candida parapsilosis and the bacterial species Staphylococcus aureus may be responsible for hospital-acquired infections in patients undergoing invasive medical interventions or surgical procedures and often coinfect critically ill patients in complicating polymicrobial biofilms. The efficacy of the re-purposing therapy has recently been reported as an alternative to be used. PUFAs (polyunsaturated fatty acids) may be used alone or in combination with currently available traditional antimicrobials to prevent and manage various infections overcoming antimicrobial resistance. The objectives of the study were to evaluate the effects of Resolvin D1 (RvD1) as an antimicrobial on S. aureus and C. parapsilosis, as well as the activity against the mixed biofilm of the same two species. Microdilution assays and time-kill growth curves revealed bacterial and fungal inhibition at minimum concentration values between 5 and 10 µg mL-1. In single-species structures, an inhibition of 55% and 42% was reported for S. aureus and C. parapsilosis, respectively. Moreover, RvD1 demonstrated an eradication capacity of 60% and 80% for single- and mixed-species biofilms, respectively. In association with the inhibition activity, a downregulation of genes involved in biofilm formation as well as ROS accumulation was observed. Eradication capability was confirmed also on mature mixed biofilm grown on silicone platelets as shown by scanning electron microscopy (SEM). In conclusion, RvD1 was efficient against mono and polymicrobial biofilms in vitro, being a promising alternative for the treatment of mixed bacterial/fungal infections.


Coinfection , Fatty Acids, Omega-3 , Humans , Staphylococcus aureus , Docosahexaenoic Acids/pharmacology , Eicosanoids , Biofilms , Candida parapsilosis
8.
Int J Mol Sci ; 24(11)2023 Jun 03.
Article En | MEDLINE | ID: mdl-37298672

Diabetic retinopathy (DR) is the most frequent microvascular retinal complication of diabetic patients, contributing to loss of vision. Recently, retinal neuroinflammation and neurodegeneration have emerged as key players in DR progression, and therefore, this review examines the neuroinflammatory molecular basis of DR. We focus on four important aspects of retinal neuroinflammation: (i) the exacerbation of endoplasmic reticulum (ER) stress; (ii) the activation of the NLRP3 inflammasome; (iii) the role of galectins; and (iv) the activation of purinergic 2X7 receptor (P2X7R). Moreover, this review proposes the selective inhibition of galectins and the P2X7R as a potential pharmacological approach to prevent the progression of DR.


Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/etiology , Neuroinflammatory Diseases , Galectins/therapeutic use , Inflammation/drug therapy , Inflammasomes/metabolism , Receptors, Purinergic P2X7 , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
9.
Biomedicines ; 11(2)2023 Feb 18.
Article En | MEDLINE | ID: mdl-36831152

BACKGROUND: Vitamin D deficiency has been associated with dry eye development during Sjögren's syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. METHODS: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C-) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). RESULTS: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C-), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. CONCLUSIONS: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.

10.
Pathog Immun ; 8(2): 16-36, 2023.
Article En | MEDLINE | ID: mdl-38223489

Background: Ureaplasma parvum (UP) is a causative agent of non-gonococcal urethritis, involved in the pathogenesis of prostatitis and epididymitis, and it could impair human fertility. Although UP infection is a frequent cause of male infertility the study evidence assessing their prevalence and the association in patients with infertility is still scarce. The molecular processes leading to defects in spermatozoa quality are not completely investigated. MicroRNAs (miRNAs) have been extensively reported as gene regulatory molecules on post-transcriptional levels involved in various biological processes such as gametogenesis, embryogenesis, and the quality of sperm, oocyte, and embryos. Methods: Therefore, the study design was to demonstrate that miRNAs in body fluids like sperm could be utilized as non-invasive diagnostic biomarkers for pathological and physiological conditions such as infertility. A post-hoc bioinformatics analysis was carried out to predict the pathways modulated by the miRNAs dysregulated in the differently motile spermatozoa. Results: Here it is shown that normospermic patients infected by UP had spermatozoa with increased quantity of superoxide anions, reduced expression of miR-122-5p, miR-34c-5, and increased miR-141-3p compared with non-infected normospermic patients. This corresponded to a reduction of sperm motility in normospermic infected patients compared with normospermic non-infected ones. A target gene prediction presumed that an essential role of these miRNAs resided in the regulation of lipid kinase activity, accounting for the changes in the constitution of spermatozoa membrane lipids caused by UP. Conclusions: Altogether, the data underline the influence of UP on epigenetic mechanisms regulating spermatozoa motility.

11.
Microorganisms ; 10(11)2022 Nov 10.
Article En | MEDLINE | ID: mdl-36363815

Ocular viral infections are common and widespread globally. These infectious diseases are a major cause of acute red eyes and vision loss. The eye and its nearby tissues can be infected by several viral agents, causing infections with a short course and limited ocular implications or a long clinical progression and serious consequences for the function and structure of the ocular region. Several surveillance studies underline the increased emergence of drug resistance among pathogenic viral strains, limiting treatment options for these infections. Currently, in the event of resistant infections, topical or systemic corticosteroids are useful in the management of associated immune reactions in the eye, which contribute to ocular dysfunction. Many cases of viral eye infections are misdiagnosed as being of bacterial origin. In these cases, therapy begins late and is not targeted at the actual cause of the infection, often leading to severe ocular compromises, such as corneal infiltrates, conjunctival scarring, and reduced visual acuity. The present study aims at a better understanding of the viral pathogens that cause eye infections, along with the treatment options available.

12.
Microorganisms ; 10(9)2022 Aug 27.
Article En | MEDLINE | ID: mdl-36144330

HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new cases exhibiting serious visual failures. Generally, the therapy uses antiviral drugs to promote healing; however, there are currently no compounds that are able to completely eradicate the virus. In addition, the phenomenon of resistance is rapidly spreading among HSV-1 strains, creating mutants developing resistance to the common antiviral drugs; therefore, deep research on this issue is warranted. The efficacy of different ophthalmic solutions already on the market was evaluated for reducing HSV-1 infection. Different plaque assays were set up on epithelial cells, revealing that two ophthalmic solutions were able to inhibit viral replication in the early stages of infection. The data were further confirmed by molecular tests analyzing the expression levels of the principal genes involved in HSV-1 infection, and a strong reduction was observed after only 1 min of eye-drop treatment. Collectively, these results suggested the use of ophthalmic solutions as potential antiviral options for the treatment of ocular herpetic infection.

13.
Microorganisms ; 10(7)2022 Jul 10.
Article En | MEDLINE | ID: mdl-35889110

The ocular microbiome is of fundamental importance for immune eye homeostasis, and its alteration would lead to an impairment of ocular functionality. Little evidence is reported on the composition of the ocular microbiota of term infants and on the impact of antibiotic prophylaxis. METHODS: A total of 20 conjunctival swabs were collected from newborns at birth and after antibiotic treatment. Samples were subjected to 16S rRNA sequencing via system MiSeq Illumina. The data were processed with the MicrobAT software and statistical analysis were performed using two-way ANOVA. RESULTS: Antibiotic prophylaxis with gentamicin altered the composition of the microbiota. In detail, a 1.5- and 2.01-fold reduction was recorded for Cutibacterium acnes (C. acnes) and Massilia timonae (M. timonae), respectively, whereas an increase in Staphylococcus spp. of 6.5 times occurred after antibiotic exposure. CONCLUSIONS: Antibiotic prophylaxis altered the ocular microbiota whose understanding could avoid adverse effects on eye health.

14.
Molecules ; 27(15)2022 Jul 26.
Article En | MEDLINE | ID: mdl-35897964

Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5-5-10 µM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 µM and 10 µM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-ß/, NF-kB p65 levels, and ROS content. Moreover, epithelial-mesenchymal transition markers were reduced by OTX008 5 µM and 10 µM. The inhibition of galectin-1 by OTX008 in DR may preserve retinal pigment epithelial cell integrity and functionality by reducing their pro-fibrotic phenotype and epithelial-mesenchymal transition phenomenon induced by diabetes.


Diabetic Retinopathy , Galectin 1 , Calixarenes , Diabetic Retinopathy/metabolism , Epithelial Cells , Epithelial-Mesenchymal Transition , Fibrosis , Glucose/metabolism , Glucose/pharmacology , Humans , Phenols , Reactive Oxygen Species/metabolism , Retinal Pigment Epithelium/metabolism , Retinal Pigments/metabolism , Transforming Growth Factor beta/metabolism
15.
Int J Mol Sci ; 23(9)2022 Apr 19.
Article En | MEDLINE | ID: mdl-35562891

The most frequent retinal diseases, such as diabetic retinopathy, age-related macular degeneration and posterior uveitis, are underlined by oxidative stress or aging-induced retinal inflammation, which contributes to vision impairing or loss. Resolution of inflammation is emerging as a critical phase able to counteract the inflammatory process leading to the progression of retinal damage. Particularly, pro-resolving mediators (PMs) play a key role in the modulation of inflammatory exudates and could be considered a new target to be investigated in different inflammatory-autoimmune pathologies. Here, we highlight the most recent studies concerning the role of the main PMs (lipoxins, resolvins, prtectins, maresins and annexins) in retinal inflammation, in order to collect the best evidence in the field of inflammatory retinal damage resolution and to propose novel pharmacological approaches in the management of the most common retinal diseases.


Lipoxins , Retinal Diseases , Docosahexaenoic Acids , Humans , Inflammation/pathology , Inflammation Mediators
16.
Transl Vis Sci Technol ; 11(3): 16, 2022 03 02.
Article En | MEDLINE | ID: mdl-35285861

Purpose: This study explored the possibility of highlighting early retinal neurovascular alterations of diabetic retinopathy (DR) by monitoring in DR patients the serum levels of microglial biomarkers ionized calcium-binding adapter molecule 1 (Iba-1), glucose transporter 5 (GLUT5), and translocator protein (TSPO), along with serum changes of the endothelial dysfunction marker arginase-1. Methods: Serum markers were determined by enzyme-linked immunosorbent assay in 50 patients: 12 non-diabetic subjects, 14 diabetic patients without DR, 13 patients with non-proliferative DR (NPDR), and 11 patients with proliferative DR (PDR). The results were correlated with hyperreflective retinal spots (HRS), observed with optical coherence tomography (OCT). Results: Although HRS were absent in diabetic patients without DR, NPDR patients showed an average of 4 ± 1 HRS, whereas the highest presence was detected in PDR patients, with 8 ± 1 HRS (P < 0.01 vs. NPDR). HRS were positively correlated (P < 0.01) with serum levels of arginase-1 (r = 0.91), Iba-1 (r = 0.96), GLUT5 (r = 0.94), and TSPO (r = 0.88). Moreover, serum proinflammatory cytokines and chemokines showed a positive correlation (P < 0.01) with HRS number and the serum markers analyzed. Conclusions: Serum markers of microglial activation positively correlate with retinal HRS in NPDR and PDR patients. Translational Relevance: These data corroborate the possibility of highlighting early retinal neurovascular changes due to diabetes by monitoring circulating microglial markers.


Calcium-Binding Proteins/blood , Diabetes Mellitus , Diabetic Retinopathy , Glucose Transporter Type 5/blood , Microfilament Proteins/blood , Arginase , Biomarkers , Diabetic Retinopathy/diagnosis , Humans , Pilot Projects , Receptors, GABA , Retina/diagnostic imaging
17.
J Clin Med ; 11(6)2022 Mar 16.
Article En | MEDLINE | ID: mdl-35329961

The Italian government on the 8th of march in response to the increased global prevalenceof severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stated a national quarantine. In this period the absence of rapid and sure screening tests for COVID-19 made necessary more attention for presence of fever in hospitalized patients, like continuous use of surgical, FFP2, and FFP3 masks (PPE) by nurses, physicians, and patients; moreover, patients visits were restricted. In this period, during the daily activities in our orthopedic department we observed an empirical decreased incidence of post-operative fever in patients admitted for trauma surgery. The aim of this study is to compare the prevalence of post-operative fever in this period with the same period in 2019. We analyzed the presence of post-operative fever in 110 patients admitted in 2020 and 129 admitted in 2019. The results show a significant decrease of the prevalence and duration of post-operative fever in patients admitted in 2020. This study evidenced that the use of PPE and limitation in external access to the hospital decrease postoperative fever in hospitalized patients undergone surgery for fracture.

19.
Front Pharmacol ; 12: 718902, 2021.
Article En | MEDLINE | ID: mdl-34603029

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.

20.
Microorganisms ; 9(8)2021 Jul 21.
Article En | MEDLINE | ID: mdl-34442628

In 2020, a global pandemic was declared following the spread of SARS-CoV-2, the pathogen responsible for COVID-19. The risk of infection is high due to the ease of transmission, which can occur orally, through droplets, or via contact with contaminated surfaces and objects. It has also been demonstrated that the ocular surface can constitute a transmission route, especially in hospital settings, where health care workers can become a dangerous source of infection. In order to increase prevention and reduce the spread of the virus on the ocular surface, the antiviral activity of already-marketed eye drops against SARS-CoV-2 was evaluated. Iodim, Ozodrop, Septavis, and Dropsept were tested against SARS-CoV-2 in plaque-assay experiments at different stimulation times. Furthermore, the expression levels of early and late genes were evaluated through molecular assays. Results indicated that three of the four ophthalmic solutions showed a considerable dose-dependent inhibition of viral replication, highlighting their use as potential antiviral drugs against SARS-CoV-2 and preventing other ocular infections.

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