RESUMO
The skin is subject to damage from the surrounding environment. The repair of skin wounds can be very challenging due to several factors such as severe injuries, concomitant infections, or comorbidities such as diabetes. Different drugs and wound dressings have been used to treat skin wounds. Tissue engineering, a novel therapeutic approach, revolutionized the treatment and regeneration of challenging tissue damage. This field includes the use of synthetic and natural biomaterials that support the growth of tissues or organs outside the body. Accordingly, the demand for polymer-based therapeutic strategies for skin tissue defects is significantly increasing. Among the various 3D scaffolds used in tissue engineering, hydrogel scaffolds have gained special significance due to their unique properties such as natural mimicry of the extracellular matrix (ECM), moisture retention, porosity, biocompatibility, biodegradability, and biocompatibility properties. First, this article delineates the process of wound healing and conventional methods of treating wounds. It then presents an examination of the structure and manufacturing methods of hydrogels, followed by an analysis of their crucial characteristics in healing skin wounds and the most recent advancements in using hydrogel dressings for this purpose. Finally, it discusses the potential future advancements in hydrogel materials within the realm of wound healing.
Assuntos
Hidrogéis , Cicatrização , Hidrogéis/uso terapêutico , Hidrogéis/química , Pele , Materiais Biocompatíveis/uso terapêutico , Materiais Biocompatíveis/química , Engenharia Tecidual/métodosRESUMO
Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.
Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Neoplasias , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias/metabolismo , Células-Tronco/metabolismo , Células-Tronco Mesenquimais/metabolismo , Comunicação Celular/fisiologiaRESUMO
Mustard agents are vesicants that were used in warfare multiple times. They are potent alkylating agents that activate cellular pathways of apoptosis, increase oxidative stress, and induce inflammation. Eyes are particularly susceptible to mustard exposure with a wide range of ocular surface damage. Three main categories of mustard-related eye injuries are acute, chronic, and delayed-onset manifestations. Mustard keratopathy (MK) is a known complication characterized by corneal opacification, ulceration, thinning, and neovascularization that can lead to severe vision loss and discomfort. Recently, a few reports demonstrated the role of senescence induction as a new pathological mechanism in mustard-related injuries that could affect wound healing. We ran the first murine model of delayed-onset MK and nitrogen mustard-induced senescence, evaluating the pathological signs of senescence in the cornea using beta-galactosidase staining. Our results suggest that nitrogen mustard exposure causes senescence in the corneal cells, which could be the underlying mechanism for chronic and late-onset ocular surface damage. We also found a significant correlation between the percentage of positive beta-galactosidase staining and the degree of fibrosis in the cornea. This provides valuable insight into the possible role of anti-senescence drugs in the near future for accelerating corneal healing and restricting fibrosis in patients with mustard keratopathy.
Assuntos
Substâncias para a Guerra Química , Doenças da Córnea , Gás de Mostarda , Humanos , Animais , Camundongos , Substâncias para a Guerra Química/toxicidade , Gás de Mostarda/toxicidade , Mecloretamina/toxicidade , Doenças da Córnea/patologia , Córnea/metabolismo , Senescência CelularRESUMO
PURPOSE: Cellular senescence is a state of permanent growth arrest whereby a cell reaches its replicative limit. However, senescence can also be triggered prematurely in certain stressors including radiation, oxidative stress, and chemotherapy. This stress-induced senescence has been studied in the context of promoting inflammation, tumor development, and several chronic degenerative diseases of aging. Emerging research has elucidated the role of senescence in various ocular diseases. METHODS: The literature search was performed using PubMed with using the query (senescence OR aging) AND (eye disease OR ocular disease OR ophthalmic disease OR cornea OR glaucoma OR cataract OR retina) on October 20th, 2022. No time restriction was proposed. Articles were excluded if they were not referenced in English. RESULTS: Overall, 51 articles regarding senescence and ocular diseases were found and summarized in this study. Several signaling pathways have been implicated in the development of senescence. Currently, senescence has been linked to various corneal and retinal pathologies, as well as cataract and glaucoma. Given the number of pathologies, senolytics, which are small molecules with the ability to selective targeting of senescent cells, can be used as therapeutic or prophylactic agents. CONCLUSIONS: Senescence has been shown to underlie the pathogenesis of numerous ocular diseases. The overall literature on senescence and ocular disease is growing rapidly. There is an ongoing debate whether or not cellular senescence detected in experiments contributes in a significant way to diseases. Research on understanding the mechanism of senescence from ocular cells and tissues is just beginning. Multiple animal models are required to test potential senolytics. Currently, no studies exist to date which have demonstrated the benefits of senolytic therapies in human studies.
RESUMO
Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown promise in promoting nerve regeneration in ocular diseases. In particular, EVs derived from MSCs have been demonstrated to promote axonal regeneration and functional recovery in various animal models of optic nerve injury and glaucoma. EVs contain various neurotrophic factors and cytokines that can enhance neuronal survival and regeneration, promote angiogenesis, and modulate inflammation in the retina and optic nerve. Additionally, in experimental models, the application of EVs as a delivery platform for therapeutic molecules has revealed great promise in the treatment of ocular disorders. However, the clinical translation of EV-based therapies faces several challenges, and further preclinical and clinical studies are needed to fully explore the therapeutic potential of EVs in ocular disorders and to address the challenges for their successful clinical translation. In this review, we will provide an overview of different types of EVs and their cargo, as well as the techniques used for their isolation and characterization. We will then review the preclinical and clinical studies that have explored the role of EVs in the treatment of ocular disorders, highlighting their therapeutic potential and the challenges that need to be addressed for their clinical translation. Finally, we will discuss the future directions of EV-based therapeutics in ocular disorders. Overall, this review aims to provide a comprehensive overview of the current state of the art of EV-based therapeutics in ophthalmic disorders, with a focus on their potential for nerve regeneration in ocular diseases.
Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Animais , Células Endoteliais , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo , Inflamação/metabolismo , Modelos AnimaisRESUMO
Corneal injuries are a major cause of blindness worldwide. To restore corneal integrity and clarity, there is a need for regenerative bio-integrating materials for in-situ repair and replacement of corneal tissue. Here, we introduce Light-curable COrnea Matrix (LC-COMatrix), a tunable material derived from decellularized porcine cornea extracellular matrix containing un-denatured collagen and sulfated glycosaminoglycans. It is a functionalized hydrogel with proper swelling behavior, biodegradation, and viscosity that can be cross-linked in situ with visible light, providing significantly enhanced biomechanical strength, stability, and adhesiveness. Cross-linked LC-COMatrix strongly adheres to human corneas ex vivo and effectively closes full-thickness corneal perforations with tissue loss. Likewise, in vivo, LC-COMatrix seals large corneal perforations, replaces partial-corneal stromal defects and bio-integrates into the tissue in rabbit models. LC-COMatrix is a natural ready-to-apply bio-integrating adhesive that is representative of native corneal matrix with potential applications in corneal and ocular surgeries.
RESUMO
Aniridia is a panocular condition characterized by impaired eye development and vision, which is mainly due to the haploinsufficiency of the paired-box-6 (PAX6) gene. Like what is seen in aniridia patients, Pax6-deficient mice Pax6Sey-Neu/+ exhibit a varied degree of ocular damage and impaired vision. Our previous studies showed that these phenotypes were partially rescued by PD0325901, a mitogen-activated protein kinase kinase (MEK or MAP2K) inhibitor. In this study, we assessed the long-term efficacy of PD0325901 treatment in retinal health and visual behavior. At about one year after the postnatal treatment with PD0325901, Pax6Sey-Neu/+ mice showed robust improvements in retina size and visual acuity, and the elevated intraocular pressure (IOP) was also alleviated, compared to age-matched mice treated with vehicles only. Moreover, the Pax6Sey-Neu/+ eyes showed disorganized retinal ganglion cell (RGC) axon bundles and retinal layers, which we termed as hotspots. We found that the PD treatment reduced the number and size of hotspots in the Pax6Sey-Neu/+ retinas. Taken together, our results suggest that PD0325901 may serve as an efficacious intervention in protecting retina and visual function in aniridia-afflicted subjects.
Assuntos
Aniridia , Fatores de Transcrição Box Pareados , Animais , Aniridia/genética , Modelos Animais de Doenças , Proteínas do Olho/genética , Haploinsuficiência , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Fator de Transcrição PAX6/genética , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/genética , RetinaRESUMO
Ocular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is currently available. The research was conducted to investigate the therapeutic potential of mesenchymal stem cell-conditioned media (MSC-CM) in NM-induced corneal wounds. NM was added to different types of corneal cells, the ocular surface of porcine, and the ocular surface of mice, followed by MSC-CM treatment. NM significantly induced apoptotic cell death, cellular ROS (Reactive oxygen species), and reduced cell viability, metabolic gene expression, and mitochondrial function, and, in turn, delayed wound healing. The application of MSC-CM post NM exposure partially restored mitochondrial function and decreased intracellular ROS generation which promoted cell survival. MSC-CM therapy enhanced wound healing process. MSC-CM inhibited NM-induced apoptotic cell death in murine and porcine corneal tissue. The application of MSC-CM following a chemical insult led to significant improvements in the preservation of corneal structure and wound healing. In vitro, ex vivo, and in vivo results suggest that MSC-CM can potentially provide targeted therapy for the treatment of chemical eye injuries, including mustard gas keratopathy (MGK) which presents with significant loss of vision alongside numerous corneal pathologies.
Assuntos
Lesões da Córnea , Células-Tronco Mesenquimais , Gás de Mostarda , Animais , Lesões da Córnea/induzido quimicamente , Lesões da Córnea/metabolismo , Lesões da Córnea/terapia , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/metabolismo , Mecloretamina/toxicidade , Células-Tronco Mesenquimais/metabolismo , Camundongos , Gás de Mostarda/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Fator de Células-Tronco/metabolismo , Suínos , CicatrizaçãoRESUMO
Conflicting results have been reported regarding the effects of 1,25 OH-vitamin D3 on corneal wound healing. Therefore, we undertook this study to determine whether the observed differences are dose related. The dose-dependent effects of 1,25 OH-vitamin D3 on corneal wound healing were evaluated using scratch assays on human corneal limbal-epithelial cells (HCLEs) and in vivo mouse corneal epithelial debridement. To evaluate the anti-inflammatory effects of 1,25 OH-vitamin D3, macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the 10-6 M, 10-7 M and 10-8 M 1,25 OH-vitamin D3. 10-7 M 1,25 OH-vitamin D3 induced faster scratch wound closure compared with the other concentrations of 1,25 OH-vitamin D3 tested (10-6 M and 10-8 M), and 0.02% ethanol as a control (85.8 ± 2.6%, 33.9 ± 6.74%, 32.6 ± 3.35%, and 31.6 ± 3.99%, respectively, P < 0.0001). Single-time treatment with 10-7 M 1,25 OH-vitamin D3 also significantly improved the healing of mouse corneal epithelial wound compared to multiple treatments and control (74.1 ± 17.3% vs. 52.4 ± 11.6% and 45.8 ± 13.4%, respectively). Polyinosinic: polycytidylic acid (poly [I:C])-stimulated macrophage cells and 10-7 M 1,25 OH-vitamin D3 significantly decreased gene expression of ICAM1, TLR3, IL6, IL8, and TNFα (P < 0.0001). Our results suggest the dose-dependent therapeutic effect of 1,25 OH-vitamin D3 in corneal wound healing which can be potentially used as a non-invasive option in the treatment of corneal wounds.
Assuntos
Calcitriol/farmacologia , Córnea/metabolismo , Cicatrização/efeitos dos fármacos , Animais , Calcitriol/metabolismo , Linhagem Celular , Colecalciferol/farmacologia , Córnea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Calcitriol/genética , Vitaminas/farmacologiaRESUMO
Macrophages are crucial drivers of inflammatory corneal neovascularization and thus are potential targets for immunomodulatory therapies. We hypothesized that therapeutic use of cornea-derived mesenchymal stromal cells (cMSCs) may alter the function of macrophages. We found that cMSCs can modulate the phenotype and angiogenic function of macrophages. In vitro, cMSCs induce apoptosis of macrophages while preferentially promoting a distinct CD14hi CD16hi CD163hi CD206hi immunophenotype that has significantly reduced angiogenic effects based on in vitro angiogenesis assays. In vivo, application of cMSCs to murine corneas after injury leads to reduced macrophage infiltration and higher expression of CD206 in macrophages. Macrophages cocultured ("educated") by cMSCs express significantly higher levels of anti-angiogenic and anti-inflammatory factors compared with control macrophages. In vivo, injured corneas treated with cMSC-educated macrophages demonstrate significantly less neovascularization compared with corneas treated with control macrophages. Knocking down the expression of pigment epithelial derived factor (PEDF) in cMSCs significantly abrogates its modulating effects on macrophages, as shown by the reduced rate of apoptosis, decreased expression of sFLT-1/PEDF, and increased expression of vascular endothelial growth factor-A in the cocultured macrophages. Similarly, cMSCs isolated from PEDF knockout mice are less effective compared with wild-type cMSCs at inhibiting macrophage infiltration when applied to wild-type corneas after injury. Overall, these results demonstrate that cMSCs therapeutically suppress the angiogenic capacity of macrophages and highlight the role of cMSC secreted PEDF in the modulation of macrophage phenotype and function. Stem Cells 2018;36:775-784.
Assuntos
Córnea/citologia , Imunomodulação/fisiologia , Macrófagos/citologia , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica , Animais , Apoptose/fisiologia , Córnea/irrigação sanguínea , Imunofenotipagem/métodos , Camundongos KnockoutRESUMO
Colonization by Staphylococcus aureus (S. aureus) has been implicated in many infectious and wound healing disorders. This study was performed to characterize the pathogenic role of S. aureus alpha-hemolysin (alpha-toxin) in corneal epithelial wound healing and infectious keratitis in the setting of a corneal wound. The effect of wild-type and isogenic Hla mutant (α-hemolysin gene deleted) S. aureus bacteria and conditioned media on corneal epithelial wound healing was tested in vitro using a scratch assay and in vivo using a murine epithelial debridement model. The invasiveness of wild-type and Hla mutant S. aureus was evaluated in vitro in human corneal epithelial cells and in vivo in a murine model of infectious keratitis following total epithelial debridement. S. aureus and its conditioned media significantly delayed epithelial wound closure both in vitro (Pâ¯<â¯0.05) and in vivo (Pâ¯<â¯0.05). The effect of S. aureus on wound healing was significantly diminished with the Hla mutant strain (Pâ¯<â¯0.05). Likewise, compared to the wild-type strain, the Hla mutant strain demonstrated significantly reduced ability to invade corneal epithelial cells in vitro (Pâ¯<â¯0.05) and infect murine corneas following total epithelial debridement in vivo (Pâ¯<â¯0.05). In conclusion, S. aureus alpha-hemolysin plays a major role in the pathologic modulation of corneal epithelial wound healing and the intracellular invasion of the bacteria. Limiting colonization by S. aureus and/or blocking alpha-hemolysin may provide a therapeutic approach for corneal wound healing and infectious disorders.
Assuntos
Doenças da Córnea/microbiologia , Epitélio Corneano/lesões , Proteínas Hemolisinas/fisiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Cicatrização/fisiologia , Animais , Doenças da Córnea/patologia , Modelos Animais de Doenças , Células Epiteliais/microbiologia , Epitélio Corneano/microbiologia , Humanos , Ceratite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas/patologiaRESUMO
PURPOSE OF REVIEW: The aim of this review is to describe the underlying mechanisms of corneal epithelial homeostasis in addition to illustrating the vital role of the limbal epithelial stem cells (LESCs) and the limbal niche in epithelial regeneration and wound healing. RECENT FINDINGS: The shedded corneal epithelial cells are constantly replenished by the LESCs which give rise to epithelial cells that proliferate, differentiate, and migrate centripetally. While some recent studies have proposed that epithelial stem cells may also be present in the central cornea, the predominant location for the stem cells is the limbus. The limbal niche is the specialized microenvironment consisting of cells, extracellular matrix, and signaling molecules that are essential for the function of LESCs. Disturbances to limbal niche can result in LESC dysfunction; therefore, limbal stem cell deficiency should also be considered a limbal niche deficiency. Current and in-development therapeutic strategies are aimed at restoring the limbal niche, by medical and/or surgical treatments, administration of trophic factors, and cell based therapies. SUMMARY: The corneal epithelium is constantly replenished by LESCs that are housed within the limbal niche. The limbal niche is the primary determinant of the LESC function and novel therapeutic approaches should be focused on regeneration of this microenvironment.
Assuntos
Células Epiteliais/fisiologia , Epitélio Corneano/fisiologia , Homeostase/fisiologia , Limbo da Córnea/fisiologia , Células-Tronco/fisiologia , Cicatrização/fisiologia , Diferenciação Celular , Proliferação de Células , Doenças da Córnea/fisiopatologia , HumanosRESUMO
We studied the reproducibility and stability of limbal stem cell deficiency (LSCD) in mice following controlled injuries to the corneal and limbal epithelia. In one method, corneal and limbal epithelia were entirely removed with a 0.5 mm metal burr. In the other, limbus to limbus epithelial removal with the burr was followed by thermal injury to the limbus. These two methods were compared with a previously published one. Unwounded corneas were used as control. The corneas were examined monthly for three months by slit lamp with fluorescein staining. Immunofluorescence staining for cytokeratin 12 and 8 on corneal wholemount and cross sections were performed to determine the phenotype of the epithelium. Mechanical shaving of the epithelium, with or without thermal injury, resulted in a reproducible state of LSCD marked by superficial neovascularization, reduce of keratin 12 expression and presence of goblet cells on the cornea. The phenotype was stable in 100% of the eyes up to at least three months. Thermal injury produced a more severe phenotype with more significant stromal opacification. These corneal injury models may be useful for studying the mechanisms leading to limbal stem cell deficiency.
Assuntos
Lesões da Córnea/patologia , Neovascularização da Córnea/patologia , Queimaduras Oculares/patologia , Limbo da Córnea/patologia , Células-Tronco/patologia , Animais , Lesões da Córnea/complicações , Neovascularização da Córnea/etiologia , Modelos Animais de Doenças , Queimaduras Oculares/complicações , Limbo da Córnea/lesões , CamundongosRESUMO
PURPOSE: To describe the clinical features and management strategies in patients whose limbal stem cell (LSC) disease reversed with medical therapy. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-two eyes of 15 patients seen at 3 tertiary referral centers between 2007 and 2011 with 3 months or more of follow-up. METHODS: Medical records of patients with medically reversible LSC disease were reviewed. Demographic data, causes, location and duration of disease, and medical inventions were analyzed. MAIN OUTCOME MEASURES: Primary outcomes assessed included resolution of signs of LSC disease and improvement in visual acuity. RESULTS: Causes of the LSC disease included contact lens wear only (13 eyes), contact lens wear in the setting of ocular rosacea (3 eyes), benzalkonium chloride toxicity (2 eyes), and idiopathic (4 eyes). Ophthalmologic findings included loss of limbal architecture, a whorl-like epitheliopathy, or an opaque epithelium arising from the limbus with late fluorescein staining. The superior limbus was the most common site of involvement (95%). The corneal epithelial phenotype returned to normal with only conservative measures, including lubrication and discontinuing contact lens wear in 4 patients (4 eyes), whereas in 11 patients (18 eyes), additional interventions were required after at least 3 months of conservative therapy. Medical interventions included topical corticosteroids, topical cyclosporine, topical vitamin A, oral doxycycline, punctal occlusion, or a combination thereof. All eyes achieved a stable ocular surface over a mean follow-up of 15 months (range, 4-60 months). Visual acuity improved from a mean of 20/42 to 20/26 (P < 0.0184). CONCLUSIONS: Disturbances to the LSC function, niche, or both may be reversible with medical therapy. These cases, which represent a subset of patients with LSC deficiency, may be considered to have LSC niche dysfunction.
Assuntos
Doenças da Córnea/terapia , Limbo da Córnea/patologia , Células-Tronco/patologia , Adulto , Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Lentes de Contato/efeitos adversos , Doenças da Córnea/patologia , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual , Vitamina A/uso terapêutico , Adulto JovemRESUMO
PURPOSE: To report a case of resolution of corneal findings in a patient with atopic keratoconjunctivitis after treatment with leflunomide. METHODS: Case report. RESULTS: A 57-year-old male presented with ocular signs and symptoms consistent with severe atopic keratoconjunctivitis. His case was distinguished by impressive sub-epithelial Salzmann-like nodules in the shape of petaloid plaques in both eyes. These keratinized plaques persisted despite topical steroids, tacrolimus ointment, and routine subconjunctival triamcinolone injections. The patient was started on leflunomide 10 mg daily for seropositive rheumatoid arthritis with rapid subsequent improvement in his symptoms, vision, and keratopathy. The patient has remained stable on oral leflunomide. CONCLUSION: To the authors' knowledge, this is the first case report to describe rapid resolution of "plaque keratopathy" and improvement of AKC with leflunomide treatment. Further work remains to be done to elucidate the role of disease-modifying drugs in atopic keratoconjunctivitis.
RESUMO
Chlorine (Cl2) exposure poses a significant risk to ocular health, with the cornea being particularly susceptible to its corrosive effects. Antioxidants, known for their ability to neutralize reactive oxygen species (ROS) and alleviate oxidative stress, were explored as potential therapeutic agents to counteract chlorine-induced damage. In vitro experiments using human corneal epithelial cells showed decreased cell viability by chlorine-induced ROS production, which was reversed by antioxidant incubation. The mitochondrial membrane potential decreased due to both low and high doses of Cl2 exposure; however, it was recovered through antioxidants. The wound scratch assay showed that antioxidants mitigated impaired wound healing after Cl2 exposure. In vivo and ex vivo, after Cl2 exposure, increased corneal fluorescein staining indicates damaged corneal epithelial and stromal layers of mice cornea. Likewise, Cl2 exposure in human ex vivo corneas led to corneal injury characterized by epithelial fluorescein staining and epithelial erosion. However, antioxidants protected Cl2-induced damage. These results highlight the effects of Cl2 on corneal cells using in vitro, ex vivo, and in vivo models while also underscoring the potential of antioxidants, such as vitamin A, vitamin C, resveratrol, and melatonin, as protective agents against acute chlorine toxicity-induced corneal injury. Further investigation is needed to confirm the antioxidants' capacity to alleviate oxidative stress and enhance the corneal healing process.
Assuntos
Antioxidantes , Lesões da Córnea , Humanos , Animais , Camundongos , Antioxidantes/metabolismo , Cloro/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Córnea/metabolismo , Fluoresceína/farmacologiaRESUMO
Polyvinyl pyrrolidone or povidone-iodine (PVP-I) is a water-soluble complex formed by the combination of iodine and a water-soluble polymer, polyvinyl pyrrolidone. This complex exerts bactericidal, fungicidal, and virucidal action by gradually releasing free iodine at the site of application to react with pathogens. In ophthalmology, PVP-I is used as a disinfectant and antiseptic agent for preoperative preparation of the skin and mucous membranes and for treating contaminated wounds. PVP-I has been shown to reduce effectively the risk of endophthalmitis in various ocular procedures, including cataract surgery and intravitreal injections; however, it has also been used in the treatment of conjunctivitis, keratitis, and endophthalmitis, with promising results especially in low-resource situations. PVP-I has been associated with complications such as postoperative eye pain, persistent corneal epithelial defects, ocular inflammation, and an attendant risk of keratitis. In cases of poor PVP-I tolerance, applying PVP-I at lower concentrations or using alternative antiseptics such as chlorhexidine should be considered. We provide an update on the efficacy of PVP-I in the prophylaxis and treatment of conjunctivitis, keratitis, and endophthalmitis and a comprehensive analysis of the current literature regarding the use of PVP-I in the management of these ocular conditions. Also, PVP-I-related adverse effects and toxicities and its alternatives are discussed. The goal is to present a thorough evaluation of the available evidence and to offer practical recommendations for clinicians regarding the therapeutic usage of PVP-I in ophthalmology.
Assuntos
Anti-Infecciosos Locais , Extração de Catarata , Conjuntivite , Endoftalmite , Iodo , Ceratite , Oftalmologia , Humanos , Povidona-Iodo/farmacologia , Povidona-Iodo/uso terapêutico , Polivinil , Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/uso terapêutico , Iodo/uso terapêutico , Endoftalmite/tratamento farmacológico , Endoftalmite/prevenção & controle , Povidona , Conjuntivite/induzido quimicamente , Conjuntivite/tratamento farmacológico , Ceratite/tratamento farmacológico , ÁguaRESUMO
Ocular trauma is an important cause of monocular blindness worldwide. Injury to the lens after blunt or penetrating trauma is common and can result in vision impairment. Selecting the most appropriate therapeutic approaches depends on factors such as patients' age, mechanism of trauma, and underlying clinical conditions. Early management, especially within childhood, is essential because of the difficulties involved in examination; anatomical variations; as well as accompanying intraocular inflammation, amblyopia, or vitreoretinal adhesions. The objective of this study was to provide a comprehensive review of the epidemiology and clinical management of traumatic cataract, highlighting the significance of accurate diagnosis and selection of the optimal therapeutic approach.
Assuntos
Catarata , Traumatismos Oculares , Cristalino , Humanos , Catarata/etiologia , Traumatismos Oculares/etiologia , Traumatismos Oculares/complicações , Traumatismos Oculares/diagnóstico , Cristalino/lesões , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico , Extração de CatarataRESUMO
PURPOSE: Clinical diagnosis of dry eye disease is based on a subjective Ocular Surface Disease Index questionnaire or various objective tests, however, these diagnostic methods have several limitations. METHODS: We conducted a comprehensive review of articles discussing various applications of artificial intelligence (AI) models in the diagnosis of the dry eye disease by searching PubMed, Web of Science, Scopus, and Google Scholar databases up to December 2022. We initially extracted 2838 articles, and after removing duplicates and applying inclusion and exclusion criteria based on title and abstract, we selected 47 eligible full-text articles. We ultimately selected 17 articles for the meta-analysis after applying inclusion and exclusion criteria on the full-text articles. We used the Standards for Reporting of Diagnostic Accuracy Studies to evaluate the quality of the methodologies used in the included studies. The performance criteria for measuring the effectiveness of AI models included area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy. We calculated the pooled estimate of accuracy using the random-effects model. RESULTS: The meta-analysis showed that pooled estimate of accuracy was 91.91% (95% confidence interval: 87.46-95.49) for all studies. The mean (±SD) of area under the receiver operating characteristic curve, sensitivity, and specificity were 94.1 (±5.14), 89.58 (±6.13), and 92.62 (±6.61), respectively. CONCLUSIONS: This study revealed that AI models are more accurate in diagnosing dry eye disease based on some imaging modalities and suggested that AI models are promising in augmenting dry eye clinics to assist physicians in diagnosis of this ocular surface condition.
RESUMO
PURPOSE: To develop an artificial intelligence (AI) model to diagnose Acanthamoeba keratitis (AK) based on in vivo confocal microscopy (IVCM) images extracted from the Heidelberg Retinal Tomograph 3 (HRT 3). METHODS: This retrospective cohort study utilized HRT 3 IVCM images from patients who had received a culture-confirmed diagnosis of AK between 2013 and 2021 at Massachusetts Eye and Ear. Two cornea specialists independently labeled the images as AK or nonspecific finding (NSF) in a blind manner. Deep learning tasks were then conducted through Python and TensorFlow. Distinguishing between AK and NSF was designed as the task and completed through a devised convolutional neural network. RESULTS: A dataset of 3312 confocal images from 17 patients with a culture-confirmed diagnosis of AK was used in this study. The inter-rater agreement for identifying the presence or absence of AK in IVCM images was 84 %, corresponding to a total of 2782 images on which both observers agreed and which were included in the model. 1242 and 1265 images of AK and NSF, respectively, were utilized in the training and validation sets, and 173 and 102 images of AK and NSF, respectively, were utilized in the evaluation set. Our model had an accuracy, sensitivity, and specificity of 76 % each, and a precision of 78 %. CONCLUSIONS: We developed an HRT-based IVCM AI model for AK diagnosis utilizing culture-confirmed cases of AK. We achieved good accuracy in diagnosing AK and our model holds significant promise in the clinical application of AI in improving early AK diagnosis.