Search Results (417)

We investigated the repeatability of the MS-39 in determining power vector components—the spherical equivalent (SEQ) and astigmatic powers (C0 and C45) and asphericity (Q)—of corneal epithelium, stroma, and endothelium in a large patient cohort. In this retrospective cross-sectional single-centre study, we evaluated a dataset containing 600 MS-39 anterior segment tomography measurements from 200 eyes (three repeat measurements each) taken prior to cataract surgery. The exported measurements included height map data for the epithelium, stroma, and endothelium surface. Model surfaces (spherocylinder (SphCyl), cylindrical conoid (CylConoid), and biconic (Biconic), all in the 3/6 mm zone) were fitted using nonlinear iterative optimisation, minimising the height difference between the measurement and model. The mean (MEAN) and standard deviation (SD) for each sequence of measurements were derived and analysed. In the 3 mm and 6 mm zone, the MEAN SEQ was 53.47/53.56/53.57 and 53.21/53.54/53.54 D for SphCyl/CylConoid/Biconic for the epithelium, −4.47/−4.51/−4.51 and −4.45/−4.50/−4.50 D for the stroma, and −6.23/−6.26/−6.26 and −6.18/−6.29/−6.30 D for the endothelium. With the three surface models and the 3/6 mm zone, the SD for SEQ/C0/C45 was in the range of 0.04 to 0.11/0.05 to 0.13/0.04 to 0.11 D for epithelium; 0.01 to 0.02/0.01 to 0.05/0.01 to 0.06 D for stroma; and 0.01 to 0.02/0.02 to 0.07/0.03 to 0.07 D for endothelium. Fitting floating model surfaces with astigmatism to map data of the corneal epithelium, stroma, and endothelium seems to be a robust and reliable method for extracting equivalent power and astigmatism using all the datapoints within a region of interest. Full article

Background: Antibody-drug conjugates (ADCs) have ushered in a new era of precision oncology by combining the targeting specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs. However, the cellular and molecular mechanisms underlying their dose-limiting ocular toxicity remain unclear. Elahere™, the first FDA-approved ADC targeting folate receptor α (FRα), demonstrates remarkable efficacy in platinum-resistant ovarian cancer but causes keratitis and other ocular toxicities in some patients. Notably, FRα is not expressed in the corneal epithelium—the primary site of damage—highlighting the urgent need to elucidate its underlying mechanisms. The aim of this study was to identify the cell-type-specific molecular mechanisms underlying Elahere-induced ocular toxicity. Methods: Sprague-Dawley rats were treated with intravenous Elahere (20 mg/kg) or vehicle weekly for five weeks. Ocular toxicity was determined by clinical examination and histopathology. Corneal single-cell suspensions were analyzed using the BD Rhapsody single-cell RNA sequencing (scRNA-seq) platform. Bioinformatic analyses to characterize changes in corneal cell populations, gene expression, and signaling pathways included cell clustering, differential gene expression, pseudotime trajectory inference, and cell-cell interaction modeling. Results: scRNA-seq profiling of 47,606 corneal cells revealed significant damage to the ocular surface and corneal epithelia in the Elahere group. Twenty distinct cell types were identified. Elahere depleted myeloid immune cells; in particular, homeostatic gene expression was suppressed in phagocytic macrophages. Progenitor populations (limbal stem cells and basal cells) accumulated (e.g., a ~2.6-fold expansion of limbal stem cells), while terminally differentiated cells decreased in corneal epithelium, indicating differentiation blockade. Endothelial cells exhibited signs of injury and inflammation, including reduced angiogenic subtypes and heightened stress responses. Folate receptor alpha, the target of Elahere, was expressed in endothelial and stromal cells, potentially driving stromal cells toward a pro-fibrotic phenotype. Fc receptor genes were predominantly expressed in myeloid cells, suggesting a potential mechanism underlying their depletion. Conclusions: Elahere induces complex, multi-compartmental ocular toxicity characterized by initial perturbations in vascular endothelial and immune cell populations followed by the arrest of epithelial differentiation and stromal remodeling. These findings reveal a cascade of cellular disruptions and provide mechanistic insights into mitigating Elahere-associated ocular side effects. Full article

Purpose: The human eye is a remarkable organ that develops from many tissues originating from neuroectodermal, ectodermal, and mesodermal sources. If any of these essential ocular tissues are impaired, it can lead to complete vision loss. Thus, the objective of these case studies is to evaluate the impact of growth factor-rich plasma (PRGF) on the healing process of corneal epithelial injuries. Methods: This case series includes three patients with corneal epithelium lesions. The patients were treated with hyaluronic acid and matrix-regenerating agent eye drops for seven days. For a minimum of six more weeks, additional cycles of PRGF eye drops were administered. Results: All three patients demonstrated improvements in visual acuity, reductions in ocular symptoms, and enhanced ocular surface health. In Patient 1, a good postoperative response was obtained after a second surgery. In Patient 2, after 30 days, the corneal leucoma showed a good response and complete recovery. In Patient 3, the ulcer and visual acuity improved 72 h after the treatment began. Conclusions: PRGF eye drops demonstrated efficacy and safety in the treatment of noninfectious corneal ulcers. Additionally, when used in conjunction with other therapies, they have the potential to augment the healing process of corneal ulcers. Full article

Background: The gut microbiota and the gut epithelium play a central role in maintaining systemic and brain homeostasis from early life. Stressful experiences during sensitive developmental windows can disrupt this balance, increasing long-term susceptibility to psychiatric disorders. However, the mechanisms through which early-life alterations in the microbiota influence brain development and function remain poorly understood. Here, the sex-specific impact of prenatal stress (PNS) on gut integrity and microbial composition in adult offspring was explored. Methods: Thirty dams were mated and randomly assigned to PNS or control. Offspring microbiota was analysed through 16S rRNA sequencing, intestinal morphology with morphometric analyses, and tight junctions using qPCR and immunofluorescence. Results: Exposure to PNS was associated with reduced intestinal surface area in males and shortened crypts in females. In both sexes, PNS caused a decrease in the expression of ZO-1, suggesting impaired gut barrier integrity. 16S rRNA sequencing revealed, furthermore, that PNS exposure was associated with a decrease in beneficial genera, including Akkermansia in males and Clostridia vadinBB60 in females, along with an increase in the pro-inflammatory genus Anaerotruncus, regardless of sex. Notably, some of these alterations were more pronounced in PNS-exposed animals that showed impaired sociability, highlighting gut microbiota inter-individual variability in the response to early-life adversity. Moreover, selected microbial changes show significant correlations with the behavioural outcomes, as well as with intestinal morphology or brain inflammatory markers. Conclusions: Together, these findings pinpoint the gut as a central player in stress vulnerability and highlight specific microbial signatures as promising biomarkers and therapeutic targets for stress-related disorders. Full article

Biological extracellular vesicles in tear fluids, such as exosomes, are thought to have physiological functions in the management of healthy ocular surface epithelium, including corneal epithelium. However, the physiological roles of tear extracellular vesicles in the ocular surface remain unclear. In this study, we investigated the physiological function of tear extracellular vesicles in mouse tear fluids in the ocular surface epithelium in vitro. Morphological analysis of the isolated extracellular vesicles from mouse tear fluids was performed using nanoparticle tracking analysis and transmission electron microscopy. The identified particles were characterised by immunoblotting for exosomal markers. After confirming the uptake of tear exosomes in cultured corneal epithelial cells, gene expression changes in mouse cultured corneal epithelial cells after tear exosome treatment were analysed. Immunostaining analysis was performed to confirm cell proliferation in the cultured corneal epithelial cells with tear exosome treatment. Tear fluids from mice contain nanoparticles with exosome-like morphologies, which express the representative exosomal markers CD9 and TSG101. The extracellular vesicles can be taken up by cultivated murine corneal epithelial cells in vitro and induce expression changes in genes related to the cell cycle, cell membranes, microtubules, and signal peptides. Treatment with the tear extracellular vesicles promoted cell proliferation of cultured murine corneal epithelial cells. Our study provides evidence that murine tear fluids contain extracellular vehicles like exosomes and they may contribute to the maintenance of the physiological homeostatic environment of the ocular surface. Full article

The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article

Lacrimal cysts (dacryops), which involve lacrimal tissue, are uncommon in dogs with an obscure/unclear pathogenesis. Compared to the current available literature, this report describes the clinicopathologic and immunohistochemical features of two cases of unusual dacryops in brachycephalic dogs. A three-year-old male Cane Corso was referred with a 1-month history of swelling ventromedial to the left eye associated with blepharospasm and epiphora. Furthermore, a severe lower and upper eyelid entropion and a deep corneal ulcer were present. B-mode ultrasonography and a CT scan revealed a subcutaneous cyst, closely adherent to the maxillary bone. Surgical removal and the correction of entropion were performed. No recurrence and/or complication was detected by seven-year follow-up. Histopathology revealed a cystic structure with single- to double-cell-layered, nonciliated, cuboidal epithelia. Alcian blue stain revealed rare, disseminated goblet cells admixed with epithelial cells. The epithelium was strongly Cytokeratin-positive by immunohistochemistry and appeared lined by several layers of smooth muscle actin (SMA)-positive myoepithelial cells. A 1-year-old male French Bulldog with a 3-month lesion of the third eyelid of the right eye. The lesion (15 mm × 7 mm) beneath the conjunctiva appeared pale-pink, smooth, and multilobulated. Excision was performed by blunt dissection through the conjunctiva on the palpebral surface of the third eyelid. Recovery was uncomplicated, and no recurrence has been noted at three-year follow-up. Cytology of the cystic fluid and histopathology and immunohistochemistry of the cyst wall revealed findings for case 1. To further characterize the SMA-positive spindle cells located directly beneath the cyst-lining epithelium, double-color immunofluorescence for SMA and p63 (a myoepithelial cell marker) was performed on the sample from case 2. The analysis revealed that the SMA-positive cells lacked p63 expression, indicating a non-myoepithelial phenotype. The histological findings in our cases are consistent with previous reports of canine dacryops. The positivity of immunohistochemical staining for SMA in cells directly beneath the epithelium of dacryops in the cases here described in two brachycephalic dogs is consistent with previous reports in dogs and horses but in contrast with a retrospective study about a human dacryops. These results support the conclusion that the pathogenesis of dacryops in dogs should exclude failure of ductular “neuromuscular” contractility. Full article

Background: PTEN is a tumor suppressor that controls many pathophysiological pathways, including cell proliferation, differentiation, apoptosis and invasiveness. Although PTEN down-modulation is a critical event in neoplastic progression, it becomes apparent that transient and local inhibition of PTEN activity might be beneficial for the healing process. Methods: In the present study, we investigated the impact of PTEN invalidation in mouse intestinal epithelium under a physiological condition and after dextran sulfate sodium (DSS) treatment to induce experimental colitis. PTEN conditional knockout was induced in intestinal epithelial cells after crossing villin-Cre and PTEN^flox/flox mice. Results: PTEN invalidation alleviates experimental colitis induced by DSS, as evidenced by decreased weight loss during the acute phase, the lower expression of inflammation markers, including the proinflammatory cytokines IFN-γ, CXCL1 and CXCL2, reduced mucosal lesions, and faster recovery after resolution of inflammation. This protective effect might result in part from the sustained proliferation of colonic epithelium, leading to hyperplasia and increased colonic crypt depth under physiological conditions, which was further exacerbated in the vicinity of mucosal injury induced by DSS treatment. Furthermore, PTEN knockout decreased paracellular permeability, thereby enhancing the intestinal barrier function. This process was associated with the reinforcement of claudin-3 immunostaining, especially on the surface epithelium of villin-Cre PTEN^flox/flox mice. Conclusions: PTEN inactivation exerts a protective effect on the onset of colitis, and the transient and local down-modulation of PTEN might constitute an approach to drive recovery following acute intestinal inflammation. Full article

The attachment of the oral epithelium to the abutment surface is crucial for the long-term success of dental implants. This study aimed to evaluate the attachment of human epithelial cells to anodized titanium surfaces. Anodized titanium discs were used as the experimental group, while machined titanium discs served as the control. Surface roughness and wettability were first measured for each group. Next, human epithelial cells were seeded onto each disc at a density of 4.0 × 10⁴ cells/cm² and evaluated 3, 6, and 24 h later for cell proliferation, as well as mRNA expression and protein levels of laminin and integrin β₄. Surface roughness was comparable between the two groups; however, wettability was significantly higher in the experimental group. Cell proliferation increased over time in both groups and showed no significant difference. Notably, the expression levels of both laminin and integrin β₄ were significantly higher in the experimental group at 24 h. Furthermore, protein localization of laminin and integrin β₄ was observed along the cell margins on the anodized surface. These findings suggest that anodization enhances epithelial cell attachment by promoting the expression and peripheral organization of key adhesion molecules. Full article

The junctional epithelium, which lines the inner gingival surface, seals the gingival sulcus to block the infiltration of food debris and pathogens. The junctional epithelium is derived from the reduced enamel epithelium, consisting of late developmental stage ameloblasts and accessory cells. No prior studies have investigated whether defective ameloblast differentiation or enamel matrix formation affects junctional epithelium anatomy or function. Here, we examined the junctional epithelium in mice exhibiting amelogenesis imperfecta due to loss-of-function mutations in the major enamel matrix protein amelogenin (Amelx^−/−) or the critical enamel matrix protease KLK4 (Klk4^−/−). Histological analyses demonstrated altered morphology and cell layer thickness of the junctional epithelium in Amelx^−/− and Klk4^−/− mice as compared to wt. Immunohistochemistry revealed reduced ODAM, laminin 5, and integrin α6, all of which are critical for the adhesion of the junctional epithelium to the enamel in Amelx^−/− and Klk4^−/− mice. Furthermore, we observed altered cell–cell adhesion and increased permeability of Dextran-GFP through the mutants’ junctional epithelium, indicating defective barrier function. Reduced β-catenin and Ki67 at the base of the junctional epithelium in mutants suggest impaired mitotic activity and reduced capacity to replenish continuously desquamated epithelium. These findings highlight the essential role of normal amelogenesis in maintaining junctional epithelium homeostasis. Full article

This review explores the potential role of topical insulin drops in corneal regeneration by analyzing the mechanism of action and clinical outcomes. Corneal integrity restoration is crucial for ocular surface healing. This review synthesizes the current literature on topical insulin for neurotrophic keratopathy (NK), highlighting its mechanism of action, therapeutic potential, and clinical outcomes. Recent studies report high rates of epithelial regeneration, suggesting that topical insulin may be an effective adjunct or alternative to conventional treatments. Further randomized controlled trials are needed to confirm its long-term efficacy and optimal dosing. Methods: Considering the limited regenerative capacity of the corneal epithelium in NK and the increasing interest in novel therapy, we review the existing literature to evaluate the role and extent of topical insulin’s contribution to corneal healing by applying the PICO framework, which allows for a clear and systematic approach to literature selection and evaluation. The literature search and study selection were conducted manually following PRISMA guidelines. Conclusions: Most of the studies resulting from the selection have small samples, and there is a lack of large, randomized clinical trials. The evidence reviewed in this study suggests that topical insulin is a promising therapy for promoting corneal healing in neurotrophic keratopathy. While clinical trials have demonstrated significant epithelial regeneration, optimal dosing and long-term safety require further investigation. Compared to conventional treatments such as autologous serum or growth factor therapy, insulin eye drops provide a cost-effective alternative. Additional research through controlled trials is needed to formulate standardized therapeutic protocols and verify long-term outcomes. Full article

Background and Clinical Significance: Brenner tumors are rare epithelial tumors that can occur in both males and females. They consist of ovarian transition cells surrounded by dense fibrous tissue and can be classified as benign, borderline, or malignant. While most commonly found in the ovary, extraovarian Brenner tumors (EOBTs) have been reported in the uterus, vagina, broad ligament, and omentum. Case Presentation: A 71-year-old postmenopausal woman presented with a polypous formation on the upper third of the posterior vaginal wall, which was found at a routine health check. Macroscopically, the lesion appeared as a solid, polypoid mass with a yellowish-gray cut surface, measuring approximately 25 × 20 mm. Histological examination revealed a polypoid formation covered by stratified squamous epithelium, with a dense fibrous stroma (Van Gieson [VG]+) and tubular structures lined by clear epithelial cells. Parenchymal cells showed low proliferative activity, with Ki-67 expression in less than 5% of cells, also Cytokeratin (CK) 7/+/p63:/+/ CK AE1/AE3: /+/ Estrogen Receptor (ER): /+/ and Progesterone Receptor (PR)/−/; CK20/-/; p53/−/, Wilms’ Tumor (WT)-1/−/; Prostate-Specific Acid Phosphatase (PSAP)/−/. The final diagnosis was an extraovarian Brenner tumor. The patient was monitored for two months post-excision, with no signs of recurrence. Conclusions: EOBTs are extremely rarely seen and vaginal involvement is far less common. Due to their rarity, these tumors may be confused with other benign or malignant vaginal lesions. In order to differentiate EOBTs from other neoplasms, histological analysis is crucial due to their characteristic transitional-type epithelium and large fibrous stroma. Further studies are required to understand the origin and clinical behavior of EOBTs. Long-term monitoring should be performed to look for any recurrence or malignant change, even though benign Brenner tumors usually have a good prognosis. Awareness of EOBTs and their possible locations is essential for accurate diagnosis and appropriate management. Full article

Background/Objectives: This study explores the ocular anatomy and glandular components of domestic dogs compared to their ancestor, the wolf, with the aim of identifying evolutionary changes due to domestication and their implications for ocular pathologies. Methods: Utilizing histological and histochemical techniques, including hematoxylin–eosin, Periodic Acid–Schiff, Alcian Blue, and lectins, this research conducts a detailed analysis of the canine and wolf ocular systems, focusing on the eyelids, tarsal glands, and conjunctival tissues. Results: There are marked histological differences between the two species, particularly in the thickness and secretion levels of the conjunctival epithelia and the structure of the tarsal glands. Dogs exhibit a thicker epithelium with greater Periodic Acid–Schiff and Alcian Blue positive secretion, suggesting enhanced ocular protection and lubrication adapted to domestic environments. Conversely, wolves display more concentrated glandular secretions and a predominance of acidic mucopolysaccharides, aligning with their adaptation to natural habitats. Conclusions: Although this study is constrained by the limited number of samples, the use of mixed dog breeds, and the focus on the Iberian wolf, it nonetheless suggests histological and evolutionary differences between domestic dogs and wolves, particularly in structures related to ocular surface protection and lubrication. These differences likely reflect adaptive responses to domestication in dogs and environmental demands in wolves. Importantly, the findings emphasize the clinical and translational potential of using dogs as comparative models for human ocular surface disorders, given their anatomical proximity to humans. Full article

Ovarian cancer (OC) is the most lethal gynecological cancer globally. Its incidence and mortality consistently rise after menopause. While parity reduces the risk of OC, nulliparity during a woman’s fertile years increases it. Although the association between reproductive history and OC risk is well-established, the long-term impact of pregnancy on the postmenopausal human ovary has received little to no attention. Parity apparently delays the natural decline of the ovarian reserve, but this association also remains unexplored to date. Based on data from cellular, biochemical, and histological markers, as well as epidemiological studies, transcriptomic analyses, and gene knockout mouse models, we review compelling evidence suggesting a critical intraovarian interplay between the residual ovarian reserve and the ovarian surface epithelium (OSE) in the aged ovary. This interaction appears to be a key factor underlying the protective effect of parity on ovarian cancer (OC) risk. We propose that functional FSHR signaling in the remnant follicles of the aged multiparous ovary somehow counteracts the oxidative stress and subsequent chronic inflammation typically observed in the senescent ovary. This mechanism would minimize DNA damage, thereby lowering the probability of neoplastic transformation in the aged mammalian ovary. The precise mechanism by which pregnancy imprints such a long-term follicle–OSE crosstalk warrants further investigation. Full article

Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is a key signaling molecule essential for eyelid closure during embryogenesis. In mice, Map3k1 knockout leads to a fully penetrant eye-open at birth (EOB) phenotype due to disrupted MAPK signaling, abnormal epithelial differentiation, and morphogenesis. To further explore the roles of MAP3K1 in ocular development, we generated a Cre-inducible gain-of-function transgenic mouse, designated as Map3k1^TG, and crossed it with Lens epithelial (Le)-Cre mice to drive MAP3K1 overexpression in developing ocular surface epithelium (OSE). Map3k1^TG;Le-Cre embryos exhibited ocular defects including premature eyelid closure, lens degeneration, and corneal edema. While corneal epithelial differentiation remained intact, the lens epithelium degenerated with lens formation compromised. Eyelid epithelium was markedly thickened, containing cells with aberrant keratin (K)14/K10 co-expression. Genetic rescue experiments revealed that Map3k1^TG;Le-Cre restored eyelid closure in Map3k1 knockout mice, whereas MAP3K1 deficiency attenuated the epithelial thickening caused by transgene expression. Mechanistically, MAP3K1 overexpression enhanced c-Jun phosphorylation in vivo and activated JNK-c-Jun, WNT, TGFβ, and Notch signaling and promoted keratinocyte proliferation and migration in vitro. These findings highlight a dose-sensitive role for MAP3K1 in regulating epithelial proliferation, differentiation, and morphogenesis during eyelid development. Full article