Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential.
Background and Objectives: Irreversible visual impairment is mainly caused by retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. Stem cell research has experienced rapid progress in recent years, and researchers and clinical ophthalmologists are trying to implement this promising technology to treat retinal degeneration. The objective of this systematic review is to analyze currently available data from clinical trials applying stem cells to treat human retinal diseases. Materials and Methods: We performed a systematic literature search in PubMed to identify articles related with stem cell therapies to retinal diseases published prior to September 2021. Furthermore, a systematic search in ClinicalTrials (NIH U.S. National Library of Medicine) was performed to identify clinical trials using stem cells to treat retinal diseases. A descriptive analysis of status, conditions, phases, interventions, and outcomes is presented here. Conclusions: To date, no available therapy based on stem cell transplantation is approved for use with patients. However, numerous clinical trials are currently finishing their initial phases and, in general, the outcomes related to implantation techniques and their long-term safety seem promising. In the next few years, we expect to see quantifiable results pertaining to visual function improvement.
Silver nanoparticles (AgNPs) play an important role in the medical field due to their potent antimicrobial activity. This, together with the constant emergence of resistance to antimicrobial drugs, means AgNPs are often investigated as an alternative to solve this problem. In this article, we analyzed the antifungal and antiamoebic effects of a recently described type of AgNP, silver nanorings (AgNRs), and compared them with other types of AgNPs. Tests of the activity of AgNPs against various fungal and amoebic species were carried out. In all cases, AgNPs showed a high biocidal effect, although with fungi this depended on the species involved. Antifungal activity was detected by the conditioning of culture media or water but this effect was not dependent on the release of Ag ions. On the other hand, the proliferation of Acanthamoeba castellanii trophozoites was reduced by silver nanorings (AgNRs) and silver nanowires (AgNWs), with AgNWs being capable of totally inhibiting the germination of A. castellanii cysts. AgNRs constitute a new type of AgNP with an antifungal and antiacanthamoebic activity. These results open the door to new and effective antimicrobial therapies as an alternative to the use of antifungals or antiamoebic drugs, thus avoiding the constant appearance of resistance and the difficulty of eradicating infections.
Small leucine-rich proteoglycans (SLRPs) regulate different processes and undergo significant alterations in various diseases. Colon carcinomas (CCs) are heterogeneous pathologies with important clinical and molecular differences depending on their location, which makes it interesting to analyze the alterations in SLRPs in right- and left-sided tumors (RS- and LSCCs). SLRP transcription levels were studied in 32 CCs using qPCR compared to healthy colon mucosae samples from the same patients, 20 of them from LSCCs and the remaining 12 from RSCCs. Protein expression of genes with significant differences in their transcriptions was analyzed by immunohistochemistry. The alterations observed were related to survival data. The arrangement of transcription of SLRPs was quite similar in ascending and descending colon, but RS- and LSCCs displayed different patterns of alteration, with a greater number of deregulations occurring in the latter. The analysis of protein expression also indicated changes in the location of these molecules, largely moving to the cell interior. While podocan underexpression showed a trend toward better outcomes, no differences were observed in terms of overall survival. In vitro studies using the HT29 tumor cell line suggest that deregulation of SLRPs could affect cell proliferation. SLRPs constitute new differential markers of RS- and LSCCs, showing differences dependent on the anatomical location of the tumor.
Background: Cell surface glycosaminoglycans (GAGs) participate in many physiological and pathological processes, including infections and inflammatory response. Acne is a common chronic inflammatory skin disorder that affects the pilosebaceous unit and has a multifactorial etiology, including bacterial colonization of the hair follicle. This study aimed to investigate the participation of GAG in the adhesion of Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis to keratinocytes and fibroblasts of the skin by competition experiments and cell surface removal using specific liases. The alteration in the transcription of the genes responsible for the synthesis of GAG induced by the adhesion of these bacteria was also analyzed by qRT-PCR. Results: GAGs are involved in bacterial adherence to skin cells, especially fibroblasts, where chondroitin sulfate displayed the higher effect. Bacterial adherence produced different alterations in the transcription of the genes responsible for GAG structures. P. acnes induced mostly changes in keratinocytes, while S. epidermidis was the main cause of alterations in fibroblasts. These variations in gene expression affected all the stages in the biosynthesis of the main species of GAGs, heparan and chondroitin sulphate. Conclusions: GAGs species are involved in the adhesion of acne-related bacteria to skin cells in a differential manner depending on each microorganism and cellular type, although other receptors seem to exist. Bacterial adherence led to variations on gene expression in skin cells affecting GAG chains structure what, consequently, should alter their interactions with different ligands, affecting the development of acne disease.
(1) Background: Abnormal corneal wound healing compromises visual acuity and can lead to neuropathic pain. Conventional treatments usually fail to restore the injured corneal tissue. In this study, we evaluated the effectiveness of a synthetic heparan sulfate mimetic polymer (HSmP) in a mouse model of corneal wound healing. (2) Methods: A surgical laser ablation affecting the central cornea and subbasal nerve plexus of mice was used as a model of the wound-healing assay. Topical treatment with HSmP was contrasted to its vehicle and a negative control (BSS). Corneal repair was studied using immunofluorescence to cell proliferation (Ki67), apoptosis (TUNEL assay), myofibroblast transformation (αSMA), assembly of epithelial cells (E-cadherin) and nerve regeneration (β-tubulin III). (3) Results: At the end of the treatment, normal epithelial cytoarchitecture and corneal thickness were achieved in HSmP-treated animals. HSmP treatment reduced myofibroblast occurrence compared to eyes irrigated with vehicle (p < 0.01) or BSS (p < 0.001). The HSmP group showed 50% more intraepithelial nerves than the BSS or vehicle groups. Only HSmP-treated corneas improved the visual quality to near transparent. (4) Conclusions: These results suggest that HSmP facilitates the regeneration of the corneal epithelium and innervation, as well as restoring transparency and reducing myofibroblast scarring after laser experimental injury.
About Me
PhD in Biology. Department of Functional Biology. Instituto Universitario Fernández-Vega, University of Oviedo.
PhD in Biology. Department of Functional Biology. Instituto Universitario Fernández-Vega, University of Oviedo.