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Cells Jun 2024Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important...
Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.
Topics: Trabecular Meshwork; Humans; MicroRNAs; Glaucoma, Open-Angle; Transforming Growth Factor beta2; Transforming Growth Factor beta; Transforming Growth Factor beta1; Cells, Cultured; Gene Expression Regulation; Intraocular Pressure
PubMed: 38920689
DOI: 10.3390/cells13121060 -
Cells Jun 2024In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant...
In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant reductions in IOP fail to completely halt its advancement. An emerging body of literature highlights the role of neuroinflammation in glaucoma. This study aimed to explore Bromfenac's anti-inflammatory properties in mitigating neuroinflammation associated with glaucoma using an ischemia-reperfusion (IR) glaucoma model. Bromfenac's impact on microglia and astrocytes under pressure was assessed via Western blotting and an enzyme-linked immunosorbent assay. Immunohistochemical staining was used to evaluate glial activation and changes in inflammatory marker expression in the IR model. Bromfenac led to the downregulation of inflammatory markers, which were elevated in the conditions of elevated pressure, and necroptosis markers were downregulated in astrocytes. In the IR model, elevated levels of GFAP and Iba-1 indicated glial activation. Following Bromfenac administration, levels of iNOS, COX-2, and PGE2-R were reduced, suggesting a decrease in neuroinflammation. Furthermore, Bromfenac administration in the IR model resulted in the improved survival of retinal ganglion cells (RGCs) and preservation of retinal function, as demonstrated by immunohistochemical staining and electroretinography. In summary, Bromfenac proved effective in diminishing neuroinflammation and resulted in enhanced RGC survival.
Topics: Bromobenzenes; Animals; Benzophenones; Reperfusion Injury; Glaucoma; Disease Models, Animal; Astrocytes; Neuroinflammatory Diseases; Retinal Ganglion Cells; Microglia; Male; Intraocular Pressure; Rats
PubMed: 38920673
DOI: 10.3390/cells13121046 -
Cells Jun 2024Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma...
Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma patients and controls and compared their characteristics with other biomarkers such as cytokines. Glaucoma patients exhibited higher exosome particle counts and smaller sizes compared to controls. Higher exosome density was correlated with more severe visual field loss. Conversely, concentrations of aqueous humor cytokines, particularly PD-L1, were primarily associated with intraocular pressure, and none of the cytokines showed a significant association with visual field damage. This may reflect the characteristics of exosomes, which are advantageous for crossing various biological barriers. Exosomes may contain more information about glaucoma functional damage occurring in the retina or optic nerve head. This highlights the potential importance of exosomes as signaling mediators distinct from other existing molecules.
Topics: Humans; Aqueous Humor; Exosomes; Biomarkers; Glaucoma; Cytokines; Female; Male; Middle Aged; Aged; Intraocular Pressure; Case-Control Studies
PubMed: 38920659
DOI: 10.3390/cells13121030 -
Cells Jun 2024Excessive levels of glutamate activity could potentially damage and kill neurons. Glutamate excitotoxicity is thought to play a critical role in many CNS and retinal...
Excessive levels of glutamate activity could potentially damage and kill neurons. Glutamate excitotoxicity is thought to play a critical role in many CNS and retinal diseases. Accordingly, glutamate excitotoxicity has been used as a model to study neuronal diseases. Immune proteins, such as major histocompatibility complex (MHC) class I molecules and their receptors, play important roles in many neuronal diseases, while T-cell receptors (TCR) are the primary receptors of MHCI. We previously showed that a critical component of TCR, CD3ζ, is expressed by mouse retinal ganglion cells (RGCs). The mutation of CD3ζ or MHCI molecules compromises the development of RGC structure and function. In this study, we investigated whether CD3ζ-mediated molecular signaling regulates RGC death in glutamate excitotoxicity. We show that mutation of CD3ζ significantly increased RGC survival in NMDA-induced excitotoxicity. In addition, we found that several downstream molecules of TCR, including Src (proto-oncogene tyrosine-protein kinase) family kinases (SFKs) and spleen tyrosine kinase (Syk), are expressed by RGCs. Selective inhibition of an SFK member, Hck, or Syk members, Syk or Zap70, significantly increased RGC survival in NMDA-induced excitotoxicity. These results provide direct evidence to reveal the underlying molecular mechanisms that control RGC death under disease conditions.
Topics: Retinal Ganglion Cells; Animals; Glutamic Acid; Signal Transduction; CD3 Complex; Mice; Mice, Inbred C57BL; N-Methylaspartate; Cell Survival; Retina; src-Family Kinases; Syk Kinase
PubMed: 38920637
DOI: 10.3390/cells13121006 -
Diseases (Basel, Switzerland) Jun 2024Recently, smell and taste disorders have seen renewed interest, as these symptoms are frequent complications of SARS-CoV-2 infection, since approximately 60% of patients... (Review)
Review
Recently, smell and taste disorders have seen renewed interest, as these symptoms are frequent complications of SARS-CoV-2 infection, since approximately 60% of patients affected by COVID-19 have shown olfactory and gustatory alterations. Otolaryngology pays attention to taste and smell abnormalities (TSAs), especially when associated with oncology. TSAs are common symptoms in people affected by cancer, yet they are ignored and underestimated. The clinical outcome of TSAs in cancer evidences the importance of identifying them with chemotherapy or radiotherapy in general, and they are associated with many types of cancer. We recognize the findings of the literature on TSAs in cancer, evaluating how it is important to consider and identify these disorders concerning reduced food enjoyment or inappropriate nutrient intake, and modulating the nutritional status, quality of life, and impact of therapy. This review aims to critically evaluate and recognize the assessment and clinical perspectives of taste and smell disorders in a cancer population.
PubMed: 38920562
DOI: 10.3390/diseases12060130 -
Diseases (Basel, Switzerland) Jun 2024Angiosarcomas are malignant vascular tumors that commonly occur on the skin of the head and neck, breast, or scalp. Oral angiosarcoma is a rare tumor (0.0077% of all...
Angiosarcomas are malignant vascular tumors that commonly occur on the skin of the head and neck, breast, or scalp. Oral angiosarcoma is a rare tumor (0.0077% of all cancers in Europe), and regarding this atypical localization, no formal treatment trials have been conducted yet. We present a case of a 58-year-old female patient with a diagnosis of oral angiosarcoma. After tumor excision was performed by transoral surgical approach, immediate reconstruction of the intraoral surgical defects was made using Integra bilayer wound collagen matrix. A skin regeneration technique has previously been reported to provide good healing for defects of buccal resection, preventing postoperative cicatricial fibrosis.
PubMed: 38920549
DOI: 10.3390/diseases12060117 -
PloS One 2024The aim of the present work is to explore the impact of the COVID-19 pandemic on research activities in a vast multidisciplinary academic community to identify the most...
PURPOSE
The aim of the present work is to explore the impact of the COVID-19 pandemic on research activities in a vast multidisciplinary academic community to identify the most critical issues.
METHOD
To this purpose we planned a survey addressed to the entire academic research staff at "Sapienza" University of Rome, which represents the largest Italian academic community. A questionnaire consisting of both open and closed-ended questions was delivered to 4118 individuals in April 2021.
RESULTS
A total of 544 responses were collected. All academic roles were sufficiently represented in the study cohort. The median number of critical issues experienced by academic research staff was three. Among these, the three most frequently reported were related to: "Access to libraries / laboratories / research sites" (21.9%), "Limitation to stay abroad / study / research periods" (17.6%), "Progress of experimental work" (14.7%), with variable prevalence according to academic position and gender. Older subjects reported issues with "Projects' financial reporting" and "Expiration of acquired consumable material more frequently". The most common critical aspects reported in relation to the economic burden were: being "Unable to allocate funds" (31.4%), a "Reduction in clinical and scientific activity" (26.3%) and experiencing "Increased expenses (comprising private costs)" (21.2%) with no differences between genders. Researchers in Applied Sciences and Natural Sciences reported a higher frequency of problems in clinical and scientific activities, whereas increased expenses were reported also by researchers operating in the Humanities field. As a possible solution aimed at improving these issues, most subjects, especially those aged >45 years, indicated "Economic aid" (22.6%), "Reduction in bureaucracy" (19.9%) or "Enhancement of the scientific and clinical activities", whereas those aged ≤45 years felt that an increased duration and better access to PhD programs were to be prioritized.
CONCLUSION
Our findings highlight the most critical issues related to research activities during the COVID-19 pandemic in a large academic community. The information achieved may be useful to identify researchers' needs and to design appropriate policies aimed at preparing research institutions for unexpected catastrophic events and limiting the negative impact on academic research activities.
Topics: Humans; COVID-19; Male; Female; Surveys and Questionnaires; Middle Aged; Adult; Italy; Pandemics; SARS-CoV-2; Universities; Aged; Biomedical Research; Research Personnel
PubMed: 38917126
DOI: 10.1371/journal.pone.0304078 -
Investigative Ophthalmology & Visual... Jun 2024To investigate the characteristics of microperimetry and optical coherence tomography (OCT) in congenital stationary night blindness (CSNB), as well as their...
PURPOSE
To investigate the characteristics of microperimetry and optical coherence tomography (OCT) in congenital stationary night blindness (CSNB), as well as their structure-function association.
METHODS
This cross-sectional study included 32 eyes from 32 participants with CSNB, comprising 18 with complete CSNB and 14 with incomplete CSNB, along with 36 eyes from 36 CSNB-unaffected controls matched for age, sex, and spherical equivalent. Using MP-3 microperimetry, central retinal sensitivity was assessed within a 20° field, distributed across six concentric rings (0°, 2°, 4°, 6°, 8°, and 10°). OCT was used to analyze retinal and choroidal thickness. The study aimed to assess the overall and ring-wise retinal sensitivity, as well as choroidal and retinal thickness in CSNB and CSNB-unaffected controls, with a secondary focus on the relationship between retinal sensitivity and microstructural features on OCT.
RESULTS
In comparison with CSNB-unaffected subjects, the overall and ring-wise retinal sensitivity as well as choroidal thickness were reduced in patients with CSNB (P < 0.001). Moreover, the central sensitivity in incomplete CSNB group was lower than in complete CSNB group (25.72 ± 3.93 dB vs. 21.92 ± 4.10 dB; P < 0.001). The retinal thickness in the CSNB group was thinner outside the fovea compared with the CSNB-unaffected group. Multiple mixed regression analyses revealed that point-to-point retinal sensitivity was significantly correlated with BCVA (P = 0.002) and the corresponding retinal thickness (P = 0.004).
CONCLUSIONS
Examination of retinal sensitivity and OCT revealed different spatial distribution profiles in CSNB and its subtypes. In CSNB eyes, retinal sensitivity on microperimetry was associated with retinal thickness on OCT.
Topics: Humans; Tomography, Optical Coherence; Female; Male; Cross-Sectional Studies; Night Blindness; Visual Field Tests; Visual Fields; Genetic Diseases, X-Linked; Retina; Adult; Myopia; Young Adult; Eye Diseases, Hereditary; Visual Acuity; Adolescent; Myopia, Degenerative; Child; Choroid
PubMed: 38916884
DOI: 10.1167/iovs.65.6.35 -
International Ophthalmology Jun 2024To evaluate the intraoperative central corneal epithelial thickness (ET) as measured by optical coherence pachymetry (OCP) in myopic eyes undergoing alcohol-assisted...
PURPOSE
To evaluate the intraoperative central corneal epithelial thickness (ET) as measured by optical coherence pachymetry (OCP) in myopic eyes undergoing alcohol-assisted photorefractive keratectomy (PRK).
METHODS
A retrospective review of patients who underwent alcohol-assisted PRK was performed. Data were abstracted on age, gender, contact lens (CL) wear, preoperative refractive errors, keratometry, topographic and ultrasonic pachymetry, and intraoperative OCP measurements before and after epithelium removal. The central ET was calculated by subtracting OCP measurement after epithelium removal from the OCP measurement prior to epithelium removal.
RESULTS
The study comprised of 162 consecutive eyes from 81 patients. Mean age was 26.73 ± 6.47 years, 50.6% were males. CL was used in 92 eyes (56.8%). The mean sphere and spherical equivalent were -3.60 ± 1.84 D and -3.26 ± 1.85D, respectively. The mean intraoperative ET was 58.22 ± 17.53 µm (range, 15-121µm). Fifty-five percent of the eyes had an ET measurement above or below the range of 40-60µm. ET was significantly higher in the second operated eye compared to the first operated eye (p = 0.006), and an association was found to CL-wear (p = 0.03). There was no significant difference in thickness between genders (p = 0.62), and no correlation to patient age (p = 0.45, r = 0.06), refractive errors (p > 0.30,r-0.07-0.08), nor keratometry(p > 0.80, r-0.01- (-0.02)).
CONCLUSION
The intraoperative assessment of ET in alcohol-assisted PRK showed a high variability of the central corneal epithelium, with a significant difference between the first and second operated eyes. This difference may have implications when the epithelium is not included in the surgical planning in surface ablation.
Topics: Humans; Photorefractive Keratectomy; Male; Female; Adult; Retrospective Studies; Epithelium, Corneal; Myopia; Young Adult; Corneal Pachymetry; Lasers, Excimer; Intraoperative Period; Tomography, Optical Coherence; Corneal Topography; Adolescent; Refraction, Ocular; Visual Acuity
PubMed: 38916805
DOI: 10.1007/s10792-024-03154-1 -
Journal of Materials Science. Materials... Jun 2024The current clinical application of glaucoma drainage devices is made of non-degradable materials. These non-degradable drainage devices often trigger inflammatory...
The current clinical application of glaucoma drainage devices is made of non-degradable materials. These non-degradable drainage devices often trigger inflammatory responses and scar proliferation, possibly leading to surgical failure. We developed a biodegradable material hydroxyapatite-coated magnesium (HA-Mg) as a glaucoma drainage device. Twelve New Zealand white rabbits were randomly assigned to three groups: HA-Mg drainage plate group (6 right eyes), trabeculectomy group (6 right eyes), and control group (12 left eyes). Results showed that all HA-Mg drainage plates were completely degraded ~4 months postoperatively. At the 5th month postoperatively, there was no statistical difference in the corneal endothelium density between the HA-Mg drainage plate group and the control group (p = 0.857). The intraocular pressure (IOP) level in the HA-Mg drainage plate implantation group was lower than in the other two groups. The trypan blue dye still drained from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation. HE staining revealed the scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded, with no obvious infiltration with the inflammatory cells. This study showed the safety and efficacy of HA-Mg glaucoma drainage plate in controlling IOP after implantation into the anterior chamber of rabbit eyes.
Topics: Animals; Rabbits; Intraocular Pressure; Glaucoma Drainage Implants; Anterior Chamber; Glaucoma; Magnesium; Durapatite; Trabeculectomy
PubMed: 38916635
DOI: 10.1007/s10856-024-06806-x