ABSTRACT
Management of infections at ocular injury often requires prolonged and high dose of antibiotic, which is associated with challenges of antibiotic resistance and bacterial biofilm formation. Tissue glues are commonly used for repairing ocular tissue defects and tissue regeneration, but they are ineffective in curing infection. There is a critical need for antibacterial ocular bio-adhesives capable of both curing infection and aiding wound closure. Herein, we present the development of an imine crosslinked N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC)silver chloride nanocomposites (QAm1-Agx) and poly-dextran aldehyde (PDA) based bactericidal sealant (BacSeal). BacSeal exhibited potent bactericidal activity against a broad spectrum of bacteria including their planktonic and stationary phase within a short duration of 4 h. BacSeal effectively reduced biofilm-embedded MRSA and Pseudomonas aeruginosa by â¼99.99 %. In ex-vivo human cornea infection model, BacSeal displayed â¼99 % reduction of ocular infection. Furthermore, the hydrogel exhibited excellent sealing properties by maintaining ocular pressure up to 75 mm-Hg when applied to human corneal trauma. Cytotoxicity assessment and hydrogel-treated human cornea with a retained tissue structure, indicate its non-toxic nature. Collectively, BacSeal represents a promising candidate for the development of an ocular sealant that can effectively mitigate infections and may assist in tissue regeneration by sealing ocular wounds.
Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Humans , Tissue Adhesives/chemistry , Tissue Adhesives/pharmacology , Biofilms/drug effects , Pseudomonas aeruginosa/drug effects , Eye Injuries/drug therapy , Cornea/drug effects , Cornea/microbiology , Microbial Sensitivity TestsABSTRACT
Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are less studied neurotrophins in the ocular surface, even though brain-derived neurotrophic factor is well characterized in glaucoma, retina, and neuroscience. Recently, neurotrophin analogs with panTrk activity and TrkC selectivity have shown promise as novel drugs for treating dry eye disease. In this review, we discuss the biology of the neurotrophin family, its role in corneal homeostasis, and its use in treating ocular surface diseases. There is an unmet need to investigate parenteral neurotrophins and its analogs that activate TrkB and TrkC selectively.
Subject(s)
Brain-Derived Neurotrophic Factor , Eye Injuries , Nerve Growth Factor , Receptor Protein-Tyrosine Kinases , Humans , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/pharmacology , Eye/metabolism , Eye/pathology , Ligands , Nerve Growth Factor/metabolism , Nerve Growth Factor/pharmacology , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Nerve Growth Factor/metabolism , Receptor, trkA/metabolism , Receptor, trkB/metabolism , Receptor, trkC/metabolism , Eye Injuries/drug therapy , Eye Injuries/genetics , Eye Injuries/metabolismABSTRACT
Purpose: Pituitary adenylate cyclase-activating polypeptide (PACAP) has shown potent neuroprotective effects in central nervous system and retina disorders. However, whether PACAP can attenuate retinal neurodegeneration induced by acute ocular hypertension (AOH) and the underlying mechanisms remain unknown. In this study, we aimed to investigate the effects of PACAP on the survival and function of retinal ganglion cells (RGCs), apoptosis, and inflammation in a mouse model of AOH injury. Methods: PACAP was injected into the vitreous body immediately after inducing AOH injury. Hematoxylin and eosin staining and optical coherence tomography were used to evaluate the loss of retina tissue. Pattern electroretinogram was used to evaluate the function of RGCs. TUNEL assay was used to detect apoptosis. Immunofluorescence and western blot were employed to evaluate protein expression levels. Results: PACAP treatment significantly reduced the losses of whole retina and inner retina thicknesses, Tuj1-positive RGCs, and the amplitudes of pattern electroretinograms induced by AOH injury. Additionally, PACAP treatment remarkably reduced the number of TUNEL-positive cells and inhibited the upregulation of Bim, Bax, and cleaved caspase-3 and downregulation of Bcl-xL after AOH injury. Moreover, PACAP markedly inhibited retinal reactive gliosis and vascular inflammation, as demonstrated by the downregulation of GFAP, Iba1, CD68, and CD45 in PACAP-treated mice. Furthermore, upregulated expression of NF-κB and phosphorylated NF-κB induced by AOH injury was attenuated by PACAP treatment. Conclusions: PACAP could prevent the loss of retinal tissue and improve the survival and function of RGCs. The neuroprotective effect of PACAP is probably associated with its potent anti-apoptotic and anti-inflammatory effects.
Subject(s)
Eye Injuries , Glaucoma , Neuroprotective Agents , Ocular Hypertension , Retinal Diseases , Animals , Anti-Inflammatory Agents/therapeutic use , Eye Injuries/drug therapy , Glaucoma/drug therapy , Inflammation/drug therapy , Intravitreal Injections , Mice , NF-kappa B , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology , Retinal Diseases/drug therapy , Retinal Diseases/etiology , Retinal Diseases/prevention & controlABSTRACT
Purpose: The purpose of this study was to explore the therapeutic role of heat shock protein 90 (Hsp90) in wound healing of injury cornea epithelium. Methods: The right eye of C57BL/6N male mice were performed the debridement wounds in the center of the cornea using an algerbrush II blade. The injured area was determined by staining the cornea with fluorescein sodium and measured with image-J. Immunoblotting, ELISA and immunochemistry were used for determining protein expression. The quantitation PCR was performed to measure mRNA expression. Results: Hsp90α is upregulated at both the mRNA and protein levels, and is secreted extracellularly into the corneal stroma and tear film during the healing process after corneal injury in mice. This upregulation is associated with activation of HSF1. Administration of recombinant exogenous Hsp90α (eHsp90α) speeds up wound healing of injured corneal epithelium. The eHsp90α binds to low-density lipoprotein (LDL)-related protein-1 (LRP-1) on the corneal epithelial cells and increases phosphorylation of AKT at S473, which is associated with proliferation and migration corneal epithelial cells in vitro or vivo. Inhibition of AKT by its inhibitor LY294002 abolishes eHsp90α-induced migration and proliferation of corneal epithelial cells. Conclusion: Hsp90α is upregulated and secreted after corneal injury and acts to promote the healing process. Recombinant Hsp90α may be a promising therapeutic drug candidate for corneal injury.
Subject(s)
Epithelium, Corneal/injuries , Eye Injuries/drug therapy , HSP90 Heat-Shock Proteins/therapeutic use , Wound Healing/drug effects , Animals , Blotting, Western , Cell Line , Cell Movement/physiology , Cell Proliferation/physiology , Debridement , Enzyme-Linked Immunosorbent Assay , Epithelium, Corneal/drug effects , Epithelium, Corneal/metabolism , Eye Injuries/metabolism , Gene Expression Regulation/physiology , HSP90 Heat-Shock Proteins/genetics , Heat Shock Transcription Factors/metabolism , Humans , Immunohistochemistry , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Male , Mice , Mice, Inbred C57BL , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Recombinant Proteins/genetics , Recombinant Proteins/therapeutic useABSTRACT
OBJECTIVE: To investigate the global practice patterns for the management of exogenous endophthalmitis. METHODS: This cross-sectional study was conducted to assess global practice patterns for the management of exogenous endophthalmitis. An online survey comprised of questions regarding the management of exogenous endophthalmitis was distributed to institutions who are members of International Globe and Adnexal Trauma Epidemiology Study Group (IGATES) or invited affiliates of the American Society of Ophthalmic Trauma and the Asia Pacific Ophthalmic Trauma Society. Responses were gathered from August 2020 to January 2021. RESULTS: Of 42 institutions, 36 responses were received (86% response rate), of which 33 (79%) were included in the analysis. Included centers were from Asia (36%), North America (36%), South America (12%), Africa (9%), Europe (3%), and Australia (3%). Oral antibiotics were administered in 19 (58%) institutions, with moxifloxacin as the preferred agent (n = 9, 27%). The preferred method for obtaining cultures was vitreous tap (n = 25, 76%). Most institutions (n = 26, 79%) routinely administered intravitreal vancomycin and ceftazidime, while intravitreal steroids were routinely administered at 11 centers (33%). Indications for performing vitrectomy included; decreased visual acuity (n = 14, 39%); all cases of exogenous endophthalmitis (n = 4, 12%); non-response to medical therapy (n = 4, 12%); or no view of the fundus (n = 4, 12%), indicating significant variation in surgical indications. More than half (n = 17, 52%) of responding institutions routinely admitted patients with exogenous endophthalmitis to the hospital. Institutions in the United States were less likely to administer oral antibiotics (27% vs. 73%, P = .024) and to admit patients (9% vs. 73%, P < .001) compared to other countries. CONCLUSIONS: This study highlights the global variations in the management of exogenous endophthalmitis, especially as it pertains to surgical indications. Further establishment of evidence-based guidelines may be beneficial to provide more uniform guidance to optimize outcomes.
Subject(s)
Endophthalmitis , Eye Infections, Bacterial , Eye Injuries , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Endophthalmitis/drug therapy , Endophthalmitis/epidemiology , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/epidemiology , Eye Injuries/drug therapy , Humans , Retrospective Studies , United States/epidemiology , Vitrectomy/methodsABSTRACT
Open globe trauma is the major cause for single eye blindness that stem from subsequent proliferative vitreoretinopathy (PVR). Though biomaterials and tissue engineering have significantly advanced drug delivery and management of human diseases, currently there is no effective drug formulation or device to pharmacologically mitigate PVR formation after open-globe eye trauma. This highlighted the challenge we are facing to bring the technology from bench to bedside. The current study reported an engineered episcleral drug film using biodegradable material, Poly(L-lactide)-co-poly(É-caprolactone), and triamcinolone acetonide (TA) as a model drug. The film can be conveniently sized into any shape to fit the configuration of the eye globe trauma and easily installed onto the ruptured sclera during primary trauma repair surgery. The film allows therapeutic TA to slow release for at least 6 months without toxicity and demonstrated a significant benefit to reduce the odds of developing severe PVR by 5.7 times when compared with a no-drug film control on a rabbit trauma PVR model. Our results suggested this micro episcleral drug film as promising drug delivery carrier for the targeted treatment of various unwanted retinal proliferation diseases.
Subject(s)
Eye Injuries , Vitreoretinopathy, Proliferative , Animals , Delayed-Action Preparations/therapeutic use , Eye Injuries/drug therapy , Rabbits , Sclera , Triamcinolone Acetonide/therapeutic use , Vitreoretinopathy, Proliferative/drug therapyABSTRACT
PURPOSE: To describe a case of traumatic hyphema in a patient with severe hemophilia A. CASE: We present a case of a 16-year-old boy with severe hemophilia A who presented to our ophthalmology department with total hyphema and elevated intraocular pressure 3 days after a history of blunt ocular trauma on his right eye. Due to the persistent intraocular pressure elevation and total hyphema despite medical intervention, an early anterior chamber washout was performed with the replacement of factor VIII preoperatively and postoperatively. Re-bleeding or any other complications were not experienced during surgery or postoperatively. At the first postoperative week, 20/20 visual acuity and a normal intraocular pressure without antiglaucoma medication was retained and remained stable during the 6-month follow-up. CONCLUSION: In such cases with hemophilia A, traumatic hyphema, and intraocular pressure elevation despite medical intervention, an early surgical clot removal under intense factor VIII replacement could be performed. In the early postoperative period, factor replacement should be resumed in order to avoid re-bleeding.
Subject(s)
Eye Injuries/diagnosis , Hemophilia A/complications , Hyphema/diagnosis , Hyphema/drug therapy , Wounds, Nonpenetrating/diagnosis , Adolescent , Anterior Chamber/drug effects , Coagulants/therapeutic use , Eye Injuries/drug therapy , Eye Injuries/etiology , Factor VIII/therapeutic use , Hemophilia A/drug therapy , Humans , Hyphema/etiology , Intraocular Pressure , Male , Visual Acuity , Wounds, Nonpenetrating/drug therapy , Wounds, Nonpenetrating/etiologyABSTRACT
Colletotrichum is a rare fungal pathogen, which is known to cause anthracnose in plants and keratitis or subcutaneous infections in humans. Among the seven Colletotrichum species reported in eye infections, truncatum species is usually virulent with poor visual prognosis even after surgical treatment. Here we report a case of Colletotrichum truncatum keratitis in a young boy with thorn injury that completely resolved with topical natamycin and voriconazole.
Subject(s)
Colletotrichum/isolation & purification , Eye Infections, Fungal/microbiology , Eye Injuries/complications , Keratitis/microbiology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents, Local/therapeutic use , Antifungal Agents/therapeutic use , Child , Colletotrichum/classification , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Eye Injuries/drug therapy , Eye Injuries/etiology , Gatifloxacin/therapeutic use , Humans , Itraconazole/therapeutic use , Keratitis/diagnosis , Keratitis/drug therapy , Male , Natamycin/therapeutic use , Visual AcuitySubject(s)
Eye Pain/etiology , Eye/diagnostic imaging , Hyphema/diagnostic imaging , Iris/pathology , Slit Lamp Microscopy/instrumentation , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Corneal Injuries/complications , Corneal Injuries/pathology , Eye/pathology , Eye Injuries/complications , Eye Injuries/drug therapy , Eye Injuries/surgery , Eye Pain/diagnosis , Humans , Hyphema/pathology , Male , Prolapse , Slit Lamp , Tomography, X-Ray Computed/methods , Vision Disorders/diagnosis , Wounds and Injuries/surgerySubject(s)
Optic Nerve Injuries/diagnosis , Adrenal Cortex Hormones/therapeutic use , Child , Decompression, Surgical , Ecchymosis/diagnosis , Ecchymosis/drug therapy , Ecchymosis/etiology , Ecchymosis/surgery , Eye Injuries/complications , Eye Injuries/diagnosis , Eye Injuries/drug therapy , Eye Injuries/surgery , Eyelid Diseases/complications , Eyelid Diseases/diagnosis , Eyelid Diseases/drug therapy , Eyelid Diseases/surgery , Humans , Male , Optic Nerve Injuries/drug therapy , Optic Nerve Injuries/etiology , Optic Nerve Injuries/surgery , Papilledema/diagnosis , Papilledema/drug therapy , Papilledema/etiology , Papilledema/surgery , Retinal Detachment/diagnosis , Retinal Detachment/drug therapy , Retinal Detachment/etiology , Retinal Detachment/surgery , Retinal Hemorrhage/diagnosis , Retinal Hemorrhage/drug therapy , Retinal Hemorrhage/etiology , Retinal Hemorrhage/surgery , Young AdultABSTRACT
BACKGROUND: To report a case of fungal keratitis caused by Colletotrichum gloeosporioides in an east coast city of China, which are rare pathogens that cause fungal keratitis in humans. METHODS: A 52-year-old man whose right eye was injured by a branch of an apple tree during farm work was referred to our Hospital. He was examined by Slit-lamp and the HRT II-RCM confocal scanning microscope, thus suggesting filamentous. Orneal scrapings were acquired and then inoculated into Sabouraud medium incubated at 28°C and 37°C. In vitro antifungal susceptibility tests were performed following the CLSI M38-A2 for Filamentous Fungi. Surgical intervention was advised because the abscess in the anterior chamber of the right eye was not completely absorbed. RESULTS: The Colletotrichum gloeosporioides isolate was identified by MALDI-TOF mass spectrometry and the BLAST after DNA sequencing of the amplified internal transcribed spacer (ITS) in rRNA. The patient's eye condition is under control and the patient's vision remains at the level of light perception (LP). CONCLUSIONS: We report the rare keratitis caused by C. gloeosporioides in eastern China, which has not been published. Suddenly ocular trauma and old surgical intervention may be the risk factors associated with Colletotrichum keratitis.
Subject(s)
Colletotrichum/isolation & purification , Eye Infections, Fungal/microbiology , Keratitis/microbiology , Antifungal Agents/therapeutic use , China , Colletotrichum/genetics , Corneal Ulcer/drug therapy , Corneal Ulcer/microbiology , Corneal Ulcer/surgery , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/surgery , Eye Injuries/complications , Eye Injuries/drug therapy , Eye Injuries/microbiology , Eye Injuries/surgery , Humans , Keratitis/diagnosis , Keratitis/drug therapy , Keratitis/surgery , Male , Malus/microbiology , Middle Aged , Mycological Typing Techniques/methods , Sequence Analysis, DNA , Trees/microbiologyABSTRACT
PURPOSE: To report a case of pediatric traumatic macular hole that closed with visual improvement after treatment with topical ketorolac. METHODS: Retrospective case report. RESULTS: A 15-year-old girl presented with persistent left blurred vision after being hit with a soccer ball 2 months before. Visual acuity was 20/40 with a full-thickness macular hole with cystoid macular edema. After treatment with ketorolac 0.4% four times a day for a month, the hole closed with resolution of the cystoid macular edema but some remaining subretinal fluid. The ketorolac was tapered over the following month, and the subretinal fluid resolved during the subsequent months. At 10 months after initial presentation, patient's vision was 20/20 with a normal foveal contour, no subretinal fluid, and minimal ellipsoid zone disruption. CONCLUSION: Topical nonsteroidal antiinflammatory drug treatment may play a role in the resolution of traumatic macular holes with cystoid macular edema.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Eye Injuries/drug therapy , Ketorolac/therapeutic use , Retinal Perforations/drug therapy , Soccer/injuries , Visual Acuity/drug effects , Wounds, Nonpenetrating/drug therapy , Administration, Ophthalmic , Adolescent , Eye Injuries/diagnostic imaging , Eye Injuries/etiology , Female , Humans , Macular Edema/diagnostic imaging , Macular Edema/drug therapy , Macular Edema/etiology , Ophthalmic Solutions , Retinal Perforations/diagnostic imaging , Retinal Perforations/etiology , Retrospective Studies , Subretinal Fluid , Tomography, Optical Coherence , Wounds, Nonpenetrating/diagnostic imaging , Wounds, Nonpenetrating/etiologyABSTRACT
BACKGROUND/PURPOSE: To document by optical coherence tomography angiography, the onset of a choroidal neovascularization (CNV) secondary to traumatic choroidal rupture and describe its changes after an intravitreal injection of bevacizumab. METHODS: Case report. RESULTS: A 20-year-old woman presented referring vision loss after a blunt ocular trauma in her left eye. The patient underwent a complete ophthalmic examination. Best-corrected visual acuity was 20/200. Fundus examination, fluorescein angiography, indocyanine green angiography, and optical coherence tomography displayed a choroidal rupture with no evidence of CNV. Optical coherence tomography angiography showed the choroidal rupture as a line of choriocapillaris rarefaction because of the mechanical damage. Six months later, best-corrected visual acuity decreased to 20/300; optical coherence tomography angiography displayed the growth of a CNV, characterized by a tangled vascular network. After one intravitreal injection of bevacizumab, optical coherence tomography angiography documented a contraction of the CNV. CONCLUSION: Optical coherence tomography angiography is a useful imaging technique for the diagnosis and follow-up of patients with choroidal ruptures. Anti-vascular endothelial growth factor agents represent an effective therapy for the treatment of CNVs secondary to this affection.
Subject(s)
Choroid/injuries , Choroidal Neovascularization/diagnosis , Eye Injuries/etiology , Rupture/etiology , Wounds, Nonpenetrating/etiology , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/etiology , Coloring Agents/administration & dosage , Eye Injuries/diagnosis , Eye Injuries/drug therapy , Female , Fluorescein Angiography , Humans , Indocyanine Green/administration & dosage , Intravitreal Injections , Rupture/diagnosis , Rupture/drug therapy , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/drug therapy , Young AdultABSTRACT
ABSTRACT Purpose: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. Methods: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. Results: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. Conclusions: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.
RESUMO Objetivos: Como uma classe de drogas psicoesti mulantes, as anfetaminas são amplamente usadas por suas propriedades estimulantes, eufóricas e alucinógenas. Muitos desses efeitos resultam de aumentos agudos na neurotransmissão da dopamina e da serotonina. Após o início desses efeitos, a 3,4-metilenedioximetanfetamina produz danos persistentes nos terminais nervosos de dopamina e serotonina, resultando em neurotoxicidade duradoura. O objetivo desta investigação foi avaliar os efeitos do tratamento baixa dose de metilenedioximetanfetamina na função da retina em camundongos C57BL/6 e seus mecanismos subjacentes. Métodos: Camundongos C57BL/6 foram divididos aleatoriamente em dois grupos (n=10): um grupo foi tratado com solução salina tamponada de fosfato por injeção intraperitoneal diária; o outro grupo foi tratado com 1 mg/kg de metilenedioximetanfetamina por injeção intraperitoneal diária durante 3 meses. Eletroretinografia foi utilizada para testar a função da retina a cada mês. A coloração H&E e análise com deoxinucleotidil terminal transferase foram utilizados para avaliar a morfologia e histologia da retina. Testes de imunoabsorção enzimática foram utilizados para medir marcadores de estresse oxidativo e fatores inflamatórios. A expressão de genes e proteínas foi detectada por PCR em tempo real e western blot. Resultados: O tratamento de três meses com metilenedioximetanfetamina induziu disfunção de retina significativa por apoptose de células fotorreceptoras por estresse oxidativo e resposta inflamatória. Conclusões: Estes resultados sugerem que o tratamento a longo prazo com metilenedioximetanfetamina aumenta as respostas inflamatórias em células fotorreceptoras, resultando em disfunção de retina em camundongos C57BL/6. Assim, a investigação foence uma justificação pré-clínica para os danos na retina causados pelo abuso de metilenedioximetanfetamina.
Subject(s)
Animals , Rats , Retinal Degeneration/drug therapy , Eye Injuries/drug therapy , N-Methyl-3,4-methylenedioxyamphetamine/toxicity , Retinal Degeneration/genetics , Eye Injuries/genetics , Blotting, Western , Apoptosis/drug effects , Oxidative Stress/drug effects , Electroretinography , Mice, Inbred C57BLABSTRACT
PURPOSE: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. METHODS: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. RESULTS: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. CONCLUSIONS: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.
Subject(s)
Eye Injuries/drug therapy , N-Methyl-3,4-methylenedioxyamphetamine/toxicity , Retinal Degeneration/drug therapy , Animals , Apoptosis/drug effects , Blotting, Western , Electroretinography , Eye Injuries/genetics , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Retinal Degeneration/geneticsSubject(s)
Blindness/etiology , Eye Injuries/complications , Optic Nerve Injuries/complications , Adolescent , Blindness/diagnosis , Blindness/drug therapy , Eye Injuries/diagnosis , Eye Injuries/drug therapy , Humans , Magnetic Resonance Imaging , Male , Methylprednisolone/therapeutic use , Optic Nerve Injuries/diagnosis , Optic Nerve Injuries/drug therapy , Papilledema/diagnosis , Papilledema/drug therapy , Papilledema/etiology , Tomography, X-Ray Computed , Visual AcuityABSTRACT
Eye trauma is a common presenting complaint in the emergency department. Correctly identifying the underlying pathology in eye trauma is critical to developing appropriate treatment plans that reduce the risk of long-term sequelae, and reduce or eliminate threats to vision. The clinical evaluation and diagnosis can be complex, and the presentation of serious eye conditions can be similar to that of more benign conditions. This article focuses on traumatic uveitis. It addresses the elements of history and examination that should suggest uveitis as the cause of pain and redness following trauma to the eye. It also outlines specific findings that can help differentiate uveitis from other causes of eye pain and redness following trauma. Included is a brief description of the pathophysiology of uveitis and the mechanism by which this inflammatory condition can result in loss of vision. Discussion includes recommended treatment. It offers a straightforward approach to making the diagnosis of traumatic uveitis.
Subject(s)
Emergency Service, Hospital , Eye Injuries/complications , Uveitis/diagnosis , Uveitis/etiology , Diagnosis, Differential , Eye Injuries/drug therapy , Eye Injuries/nursing , Female , Humans , Middle Aged , Uveitis/drug therapy , Uveitis/nursingSubject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Choroid/injuries , Choroidal Neovascularization/drug therapy , Eye Injuries/drug therapy , Adult , Aged , Child , Choroidal Neovascularization/etiology , Choroidal Neovascularization/physiopathology , Eye Injuries/etiology , Eye Injuries/physiopathology , Female , Humans , Intravitreal Injections , Male , Middle Aged , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology , Young AdultABSTRACT
Purpose/Aim: Corneal abrasions and nonhealing corneal epithelial defects are common conditions that cause pain and sometimes are slow to heal. Histatins, a family of histidine-rich peptides, have been implicated in oral and skin epithelial wound healing, and have been shown to be effective in vitro in human corneal epithelial cells. The objective of this study was to test the efficacy of histatin-1 on corneal epithelial wound healing in rabbits. MATERIALS & METHODS: Twenty-two (22) rabbits were separated into four treatment groups, each containing 3-7 rabbits. Treatments included three histatin-1 formulations (0.1 ug/ml. 1 ug/ml, and 10 ug/ml) and one inactive vehicle, one drop given three times per day. Eight (8) mm circular wounds were created using 0.5 ml of 20% ethyl alcohol in the right eye of each rabbit. A masked observer photographed each eye twice daily using slit-lamp biomicrophotography. Wound area was analyzed by using ImageJ. Statistical analysis was conducted using Graphpad Prism. RESULTS: Wound recovery was faster in animals given 0.1 ug/ml, 1 ug/ml, and 10 ug/ml when compared to the vehicle solution at 6, 24, and 30 hours after wound creation (p < 0.01). No adverse events were observed in any eyes. When analyzing area under the curve, % recovered area was higher overall in the 0.1 ug/ml (p < 0.01), 1 ug/ml (p < 0.01), and 10 ug/ml (p < 0.001) groups when compared to the vehicle solution. Hourly healing rate was also observed to be faster in the 0.1 ug/ml, 1 ug/ml, and 10 ug/ml groups (p < 0.001) at 24 hours postinjury suggesting an accelerated healing process as compared to the vehicle group. CONCLUSION: This study represents the first in vivo experiment evaluating and confirming the efficacy of topical histatin on the corneal epithelium wound healing. Further studiesare warranted to better understand the mechanism and safety of topical histatin-1 in corneal epithelial wound-healing and its potential role for human disease treatment.