To evaluate the ABCD grading system in pediatric keratoconus.
A retrospective cohort analysis of all children with keratoconus followed up at the Shamir medical center between 2010 and 2017. A ...recommendation by the treating physician to undergo corneal crosslinking (CXL) was used as an estimate for clinically significant disease progression. The ABCD grading was not available to the treating physician and was computed post hoc. The ABCD grading was compared between patients who required CXL with those who did not. A single eye of each patient was included.
Fifty eyes of 50 children were analyzed. The mean age at presentation was 15.56 ± 1.36 years. In 23 eyes, progression of keratoconus was recorded and CXL was performed (CXL-group). On presentation, the stable and CXL groups did not differ significantly in their clinical parameters. In the CXL-group, a statistically significant increase was seen in the ABCD staging (P < 0.001). In the stable group, the ABCD staging did not change significantly in parallel visits (P = 0.87). An increase of 1 point in the sum of the ABCD staging showed a 5-fold risk for undergoing CXL (odds ratio = 5.28; 95% CI, 1.82-15.34). There was no significant change in the Amsler-Krumeich classification in the CXL group.
Among a cohort of pediatric patients with keratoconus, worsening in the ABCD grading was associated with disease progression, whereas no significant change was demonstrated in the Amsler-Krumeich classification The ABCD grading system is a useful tool for initial assessment of disease progression in the pediatric population, in which early recognition is of paramount importance.
Engineered corneal endothelial grafts able to provide numerous functional endothelial cells for the restoration of corneal transparency would be a worthwhile way of replacing donor tissue, which is ...extremely scarce. The grafts are simply constructed: a biocompatible thin and transparent carrier colonized by a monolayer of cultured endothelial cells (ECs). Here we describe a process able to obtain appropriate carriers by recycling human corneas unsuitable for graft in their original state, but liable to provide multiple thin lamellae when cut with a femtosecond laser as used in refractive surgery.
We selected a robust method of stromal decellularization. To demonstrate that neither this process nor long-term storage hindered cell adherence, lamellae were endothelialized with an EC line.
The constructs achieved up to very high EC density (the main quality criterion for regular donor corneas) while remaining transparent and thin. We verified that they could be inserted in the anterior chamber of a human eye, like a conventional endothelial graft. Human decellularized cornea will likely be directly compatible with the recipient cornea and comply with the requirements of health regulatory authorities.
This study demonstrates that thin human corneal lamellae could have high potential as carriers in next-generation therapy for endothelial dysfunctions.
To evaluate the outcomes of treating deep recalcitrant fungal keratitis with intrastromal voriconazole injection.
Twenty-five patients with culture proven fungal keratitis, not responding to a ...combination of topical 5% natamycin and 1% voriconazole were treated with intrastromal voriconazole (50 µg/0.1 mL) injected in five divided doses around the infiltrate to form a depot of the drug around the circumference of the lesion.
The mean age of the patients was 52.52±12.21 years and mean time to presentation was 17.12±13.75 days from the onset of symptoms. The mean area of the infiltrate was 30.41±17.2 mm(2), hypopyon was present in 88% and all cases had infiltrates that extended beyond the mid-stromal level. Intrastromal voriconazole helped to resolve the infection in 18 (72%) patients and about 15% of these needed more than one injection. Smaller ulcers responded better to treatment. Fusarium spp were responsible for six of the seven cases that failed treatment.
Targeted delivery of voriconazole by intrastromal injection (50 µg/0.1 mL) is a safe and effective way to treat deep recalcitrant fungal keratitis, though some may need repeated injections. Fusarium keratitis may show suboptimal response but this needs further study.
Hydrogen sulfide gas (H2S) is a chemical weapon and a common environmental pollutant. H2S intoxication is lethal to humans and animals. H2S contact to the eye can cause vision loss. However, the ...molecular mechanisms associated with H2S toxicity to the cornea remain unclear, and no specific therapy exists to mitigate ocular damage from H2S. Here, we report H2S‐induced cytotoxicity and the parameters contributing to the molecular mechanisms associated with corneal toxicity using primary human corneal stromal fibroblasts (hCSFs) in vitro. Sodium hydrosulfide (NaSH) was used as a source of H2S, and the cytotoxicity of H2S was determined by treating hCSF cells with varying concentrations of NaSH (0–10 mM) for 0–72 hours. Changes in cell proliferation, oxidative stress factors, and the expression of inflammatory and fibrotic genes were studied using standard commercial kits and qRT‐PCR. NaSH exposure to hCSFs showed dose‐ and time‐dependent cytotoxicity. The IC50 of NaSH was determined to be 5.35 mM. NaSH 5.35 mM exposure led to significantly decreased cytochrome c oxidase activity, increased ROS production, and increased expression of inflammatory and fibrotic genes in hCSF cells. H2S/NaSH exposure alters normal mitochondrial function, oxidative stress, and inflammatory and fibrotic gene responses in corneal stromal fibroblasts in vitro.
Hydrogen sulfide gas (H2S) is a chemical weapon and a common environmental pollutant. H2S intoxication is lethal to humans and animals. H2S contact to the eye can cause vision loss. Here, we report dose‐ and time‐dependent cytotoxicity of H2S gas exposure to human corneal stromal fibroblasts and parameters contributing to the mechanism associated with H2S toxicity to the human cornea using an in vitro model.
Tumour progression is dependent on the interaction between tumour cells and cells of the surrounding microenvironment. The tumour is a dynamic milieu consisting of various cell types such as ...endothelial cells, fibroblasts, cells of the immune system and mesenchymal stem cells (MSCs). MSCs are multipotent stromal cells that are known to reside in various areas such as the bone marrow, fat and dental pulp. MSCs have been found to migrate towards inflammatory sites and studies have shown that they also migrate towards and incorporate into the tumour. The key question is how they interact there. MSCs may interact with tumour cells through paracrine signalling. On the other hand, MSCs have the capacity to differentiate to various cell types such as osteocytes, chondrocytes and adipocytes and it is possible that MSCs differentiate at the site of the tumour. More recently it has been shown that cross-talk between tumour cells and MSCs has been shown to increase metastatic potential and promote epithelial-to-mesenchymal transition. This review will focus on the role of MSCs in tumour development at various stages of progression from growth of the primary tumour to the establishment of distant metastasis.
Pancreatic ductal adenocarcinoma (PDAC) is considered to be a highly immunosuppressive and heterogenous neoplasm. Despite improved knowledge regarding the genetic background of the tumor and better ...understanding of the tumor microenvironment, immune checkpoint inhibitor therapy (targeting CTLA4, PD1, PDL1) has not been very successful against PDAC. The robust desmoplastic stroma, along with an extensive extracellular matrix (ECM) that is rich in hyaluronan, plays an integral role in this immune evasion. Hexosamine biosynthesis pathway (HBP), a shunt pathway of glycolysis, is a metabolic node in cancer cells that can promote survival pathways on the one hand and influence the hyaluronan synthesis in the ECM on the other. The rate-limiting enzyme of the pathway, glutamine-fructose amidotransferase 1 (GFAT1), uses glutamine and fructose 6-phosphate to eventually synthesize uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). In the current manuscript, we targeted this glutamine-utilizing enzyme by a small molecule glutamine analog (6-diazo-5-oxo-l-norleucine DON). Our results showed that DON decreased the self-renewal potential and metastatic ability of tumor cells. Further, treatment with DON decreased hyaluronan and collagen in the tumor microenvironment, leading to an extensive remodeling of the ECM and an increased infiltration of CD8+ T cells. Additionally, treatment with DON sensitized pancreatic tumors to anti-PD1 therapy, resulting in tumor regression and prolonged survival.
Spermatogenesis is fundamental to the establishment and maintenance of male reproduction, whereas its abnormality results in male infertility. Somatic cells, including Leydig cells, myoid cells, and ...Sertoli cells, constitute the microenvironment or the niche of testis, which is essential for regulating normal spermatogenesis. Leydig cells are an important component of the testicular stroma, while peritubular myoid cells are one of the major cell types of seminiferous tubules. Here we addressed the roles and mechanisms of Leydig cells and myoid cells in the regulation of spermatogenesis. Specifically, we summarized the biological features of Leydig cells and peritubular myoid cells, and we introduced the process of testosterone production and its major regulation. We also discussed other hormones, cytokines, growth factors, transcription factors and receptors associated with Leydig cells and myoid cells in mediating spermatogenesis. Furthermore, we highlighted the issues that are worthy of further studies in the regulation of spermatogenesis by Leydig cells and peritubular myoid cells. This review would provide novel insights into molecular mechanisms of the somatic cells in controlling spermatogenesis, and it could offer new targets for developing therapeutic approaches of male infertility.
Fibroblast activation protein-α (FAP) is a type-II transmembrane serine protease expressed almost exclusively to pathological conditions including fibrosis, arthritis, and cancer. Across most cancer ...types, elevated FAP is associated with worse clinical outcomes. Despite the clear association between FAP and disease severity, the biological reasons underlying these clinical observations remain unclear. Here we review basic FAP biology and FAP’s role in non-oncologic and oncologic disease. We further explore how FAP may worsen clinical outcomes via its effects on extracellular matrix remodeling, intracellular signaling regulation, angiogenesis, epithelial-to-mesenchymal transition, and immunosuppression. Lastly, we discuss the potential to exploit FAP biology to improve clinical outcomes.
To investigate corneal epithelial thickness changes during a 6-month follow-up period after transepithelial photorefractive keratectomy (tPRK), femtosecond laser-assisted laser in situ keratomileusis ...(FS-LASIK), and small incision lenticule extraction (SMILE).
This prospective study included 76 eyes of 76 participants who underwent myopic refractive surgery (23 FS-LASIK, 22 SMILE, and 31 tPRK). Epithelial thickness and anterior curvature were averaged over 4 regions (subdivided into 25 areas) and measured by spectral-domain optical coherence tomography and Scheimpflug tomography before the operation (pre) and at 1 or 3 days (pos1-3d), 1 week (pos1w), and 1 month (pos1m), 3 months (pos3m), and 6 months (pos6m) postoperatively.
The epithelial thickness of the three groups was similar in both the pre and pos6m (all
> .05), but the tPRK group fluctuated the most during the follow-up period. The largest increase was in the inferior-temporal paracentral area (7.25 ± 2.58 μm for FS-LASIK; 5.79 ± 2.41 μm for SMILE; 4.88 ± 5.84 μm for tPRK; all
< .001). Only the epithelial thickness of tPRK increased from pos3m to pos6m (
< .05), whereas all changes for FS-LASIK and SMILE were not significant (
> .05). A positive correlation of thickness changes with curvature gradient in the paracentral region of tPRK was found (
= 0.549,
= .018), but not in other regions in all groups.
Epithelial remodeling followed different trends after different surgeries from the early postoperative stage onward, but exhibited similar values at pos6m. Although remodeling after FS-LASIK and SMILE stabilized by pos3m, it remained unstable at pos6m after tPRK. These changes may affect corneal profile and lead to deviation from the intended surgical outcome.
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