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1.
Asia Pac J Ophthalmol (Phila) ; 10(2): 142-145, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33793439

RESUMO

ABSTRACT: Ophthalmologists and patients have an inherent increased risk for transmission of SARS-CoV-2. The human ocular surface expresses receptors and enzymes facilitating transmission of SARS-CoV-2. Personal protective equipment alone provides incomplete protection. Adjunctive topical ocular, nasal, and oral antisepsis with povidone iodine bolsters personal protective equipment in prevention of provider-patient transmission of SARS-CoV-2 in ophthalmology.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Desinfecção/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Transmissão de Doença Infecciosa do Profissional para o Paciente/prevenção & controle , Povidona-Iodo/uso terapêutico , Administração Oftálmica , Humanos , Soluções Oftálmicas , Equipamento de Proteção Individual , Exame Físico
2.
Zhonghua Yan Ke Za Zhi ; 57(4): 299-304, 2021 Apr 11.
Artigo em Chinês | MEDLINE | ID: mdl-33832055

RESUMO

Atropine is a classical drug with a wide use in clinical practice. In ophthalmology, atropine can be used for cycloplegia before optometry, and the treatment of amblyopia, iridocyclitis, malignant glaucoma, etc. In recent years, the "old drugs with new application " research and application of atropine for myopia prevention and control has become a hotspot and the efficacy of atropine has been preliminarily recognized. However, before the widely used in clinical, the safety of atropine draws attention. Researches concerning side effects of atropine were searched. The most common problem is photophobia due to dilated pupils, followed by poor near visual acuity, allergy and inflammation, local irritation. Other side effects include withdraw rebound, dry eyes, elevation of intraocular pressure, system reactions, photic damage and toxicity. Among them, some side effects are theoretical yet, and the long-term effects of some side reactions are not clear. Further research and exploration is needed to serve clinical evidence. At present, investigational usage for myopia prevention and control in clinical trials of atropine can be beneficial. Safety observation and efficacy evaluation are equally important in the course of application. (Chin J Ophthalmol, 2021, 57: 299-304).


Assuntos
Ambliopia , Miopia , Optometria , Atropina/efeitos adversos , Progressão da Doença , Humanos , Midriáticos/efeitos adversos , Miopia/tratamento farmacológico , Miopia/prevenção & controle , Soluções Oftálmicas
4.
AAPS PharmSciTech ; 22(3): 107, 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33719019

RESUMO

Ophthalmic diseases represent a significant problem as over 2 billion people worldwide suffer from vison impairment and blindness. Eye drops account for around 90% of ophthalmic medications but are limited in success due to poor patient compliance and low bioavailability. Low bioavailability can be attributed to short retention times in the eye caused by rapid tear turnover and the difficulty of drug diffusion through the multi-layered structure of the eye that includes lipid-rich endothelial and epithelial layers as well as the stroma which is high in water content. In addition, there are barriers such as tight junctional complexes in the corneal epithelium, lacrimal turnover, nasolacrimal drainage, blinking reflexes, efflux transporters, drug metabolism by ocular enzymes, and drug binding to or repulsion from conjunctival mucins, tear proteins, and melanin. In order to maximize transport through the cornea while minimizing drug loss through other pathways, researchers have developed numerous methods to improve eye drop formulations including the addition of viscosity enhancers, permeability enhancers, mucoadhesives, and vasoconstrictors, or using formulations that include puncta occlusion, nanocarriers, or prodrugs. This review explains the mechanism behind each of these methods, examines their history, analyzes previous and current research, evaluates future applications, and discusses the pros and cons of each technique.


Assuntos
Administração Oftálmica , Composição de Medicamentos/métodos , Soluções Oftálmicas/síntese química , Soluções Oftálmicas/farmacocinética , Animais , Disponibilidade Biológica , Córnea/efeitos dos fármacos , Córnea/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Humanos , Soluções Oftálmicas/administração & dosagem , Pró-Fármacos/administração & dosagem , Pró-Fármacos/síntese química , Pró-Fármacos/farmacocinética , Viscosidade
5.
Carbohydr Polym ; 260: 117800, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712148

RESUMO

Topical drug delivery system to the posterior segment of the eye is facing many challenges, such as rapid drug elimination, low permeability, and low concentration at the targeted sites. To overcome these challenges, Multifunctional nanocomposite eye drops of dexamethasone-carboxymethyl-ß-cyclodextrin@layered double hydroxides-glycylsarcosine (DEX-CM-ß-CD@LDH-GS) were developed for relay drug delivery. Herein, our studies demonstrated that DEX-CM-ß-CD@LDH-GS could penetrate through human conjunctival epithelial cells with an intact structure and exhibited integrity in the sclera of rabbits' eyes with in vivo fluorescence resonance energy transfer imaging. Consequently, tissue distribution indicated that DEX-CM-ß-CD@LDH-GS nanocomposite eye drops could maintain the effective therapeutic concentration of DEX in choroid-retina within 3 h. As a relay drug delivery system, drug-CD@LDH nanocomposites offer an efficient strategy for drug delivery from ocular surface to the posterior segment.


Assuntos
Dexametasona/química , Portadores de Fármacos/química , Hidróxidos/química , Nanocompostos/química , Soluções Oftálmicas/química , beta-Ciclodextrinas/química , Animais , Córnea/efeitos dos fármacos , Dexametasona/metabolismo , Dexametasona/farmacologia , Dipeptídeos/química , Liberação Controlada de Fármacos , Imagem Óptica/métodos , Coelhos
6.
Vestn Oftalmol ; 137(1): 78-82, 2021.
Artigo em Russo | MEDLINE | ID: mdl-33610154

RESUMO

Persistent corneal graft erosion or persistent epithelial corneal defect is a frequent complication of penetrating keratoplasty. Its development can be contributed by the dry eye syndrome, rare blinking, lagophthalmos, symblepharon, viral infection, autoimmune aggression, and the use of epithelial-toxic eye drops. The article presents three clinical observations of patients who developed persistent corneal graft erosion after penetrating keratoplasty. Due to the ineffectiveness of local conservative therapy for more than 3 weeks, anterior stromal corneal micropuncture was performed. After the procedure, there was a gradual epithelial proliferation, complete healing of the corneal surface was observed 10-16 days after the manipulation, the follow-up period was at least 1 year. The mechanism of action of stromal micropuncture is associated with the creation of a porous surface with better adhesion properties, as well as with the activation of the production of extracellular matrix glycoproteins such as fibronectin, type IV collagen and laminin, which are necessary for stable adhesion of the epithelium. The use of stromal micropuncture of the donor flap in the treatment of post-keratoplasty persistent corneal epithelial defect was proposed for the first time.


Assuntos
Doenças da Córnea , Transplante de Córnea , Doenças da Córnea/diagnóstico , Doenças da Córnea/etiologia , Doenças da Córnea/cirurgia , Humanos , Ceratoplastia Penetrante/efeitos adversos , Soluções Oftálmicas , Punções
7.
Medicine (Baltimore) ; 100(3): e24139, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546027

RESUMO

ABSTRACT: To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) in photorefractive keratectomy (PRK) versus Mitomycin C (MMC).This is a comparative, longitudinal and retrospective case-control study (MMC vs PRGF), in patients with a spherical correction from -0.25 to -8.00 D and cylinder correction from -0.25 to -3.00. The uncorrected distance visual acuity (UDVA), refractive efficacy and safety indices, and changes in endothelial cell density were evaluated. The predictability was assessed with the postoperative manifest spherical equivalent.Forty-four patients (72 eyes) were treated with MMC and twenty-five patients (45 eyes) with PRGF. The final UDVA (LogMar) in MMC was 0.029 ±â€Š0.065 and in PRGF it was 0.028 ±â€Š0.048 (p = 0.383). The efficacy index for MMC was 0.98 ±â€Š0.10 and 1.10 ±â€Š0.46 for patients treated with PRGF (p = 0.062). The safety index for MMC was 1.03 ±â€Š0.11 and 1.12 ±â€Š0.46 (p = 0.158) for PRGF group. The change percentage of endothelial cell density was 0.9 ±â€Š11.6 for MMC and 4.3 ±â€Š13.1 for PRGF (p = 0.593). The predictability for MMC was 92.1% and for the PRGF was 91.9% (p = 0.976). Hyperemia, eye pain and superficial keratitis were observed in 11.1% of the MMC group; no adverse events were observed with the PRGF.The use of PRGF in PRK surgery is as effective as MMC. The PRGF shows a better safety profile than MMC for its intraoperative use in PRK.


Assuntos
Transfusão de Sangue Autóloga/métodos , Opacidade da Córnea/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Ceratectomia Fotorrefrativa , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Antibióticos Antineoplásicos/uso terapêutico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mitomicina/uso terapêutico , Soluções Oftálmicas , Estudos Retrospectivos , Adulto Jovem
8.
Int J Nanomedicine ; 16: 1067-1081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603369

RESUMO

Background: Extracellular vesicles (EVs) are capable of manipulating cellular functions for the maintenance of biological homeostasis and disease progression, such as in glaucoma disease. These nano-particles carry a net negative surface charge under physiological conditions that can contribute to EVs:EVs interaction and their uptake by target cells. Purpose: To investigate the effect of glaucoma drugs on EVs physicochemical characters and the implications for their uptake by trabecular meshwork (TM) cells. Methods: TM or non-pigmented ciliary epithelium (NPCE) cells derived EVs were incubated with commercial anti-glaucoma formulation, Timolol maleate, Brinzolamide or Benzalkonium Cl and their size and zeta potential (ZP) and physical interactions of EVs derived from NPCE cells and TM cells were evaluated. The contribution of EVs interactions to up-take by TM cells was examined using fluorescence-activated cell sorting. Results: EVs size and ZP were affected by the ionic strength of the buffer rather than EVs type. Commercial glaucoma eye drops, including ß-blocker, α-2-agonist and prostaglandin analogs, reduced NPCE EVs ZP, whereas exposure of EVs to carbonic anhydrase inhibitor caused an increase in the ZP. A correlation was found between increased ZP values and increased NPCE EVs uptake by TM cells. We were able to show that Benzalkonium chloride stands behind this ZP effect and not Timolol or Brinzolamide. Conclusion: Altogether, our findings demonstrate that EVs size, surface membrane charge, and ionic strength of the surrounding have an impact on EVs:EVs interactions, which affect the uptake of NPCE EVs by TM cells.


Assuntos
Agonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Células Epiteliais/fisiologia , Vesículas Extracelulares/fisiologia , Glaucoma/tratamento farmacológico , Soluções Oftálmicas/farmacologia , Malha Trabecular/fisiologia , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Glaucoma/patologia , Humanos , Malha Trabecular/efeitos dos fármacos
10.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541940

RESUMO

A 25-year-old man presented with decreased vision in both eyes, approximately 4 years following bilateral bright ocular cosmetic iris implantation. On examination, he was found to have bilateral elevated intraocular pressures, anterior chamber cells and flare, chronic peripheral anterior synechiae and significantly reduced endothelial cell counts. Ultrasound biomicroscopy demonstrated compression of the peripheral iris, resulting in synechial angle closure in both eyes. Surgical removal of the implants was performed without additional complication. On removal, bilateral iris atrophy was evident with non-reacting pupils and permanent mydriasis. Optical coherence tomography angiography showed a reduction in iris vasculature density that is more pronounced in the area of the iris atrophic defects. This case suggests that cosmetic iris implants may compress iris vasculature, resulting in decreased iris perfusion resulting in atrophic mydriasis and iris defects. This is a potential novel mechanism for complications in eyes with cosmetic iris implants.


Assuntos
Pressão Intraocular , Doenças da Íris/complicações , Iris/cirurgia , Midríase/diagnóstico , Próteses e Implantes/efeitos adversos , Acetaminofen/uso terapêutico , Acetazolamida/uso terapêutico , Administração Intravenosa , Adulto , Analgésicos não Entorpecentes/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Humanos , Latanoprosta/uso terapêutico , Masculino , Soluções Oftálmicas/uso terapêutico , Tomografia de Coerência Óptica
11.
Yakugaku Zasshi ; 141(1): 35-39, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33390445

RESUMO

Eyedrops often contain additives other than active pharmaceutical ingredients, such as preservatives. The most frequently used preservative is benzalkonium chloride (BAC). When the ocular surface is exposed to eyedrops, the active pharmaceutical ingredients and additives can cause corneal epithelial disorder. Particularly in clinical settings, there is great interest in corneal epithelial disorders resulting from the use of glaucoma eyedrops, which is inevitable when instilled for a long period of time after the onset of disease. At the authors' institute, glaucoma is treated with consideration of reducing corneal epithelial disorder while ensuring the effect of lowering intraocular pressure by the appropriate choice of eyedrops. In this review, we show the examples of the retrospective studies. Sodium hyaluronate eyedrops are prescribed for corneal epithelial disorders such as superficial punctate keratitis associated with dry eye. Prescribable concentrations of sodium hyaluronate in Japan are 0.1% or 0.3%, and the 0.3% formulation does not contain BAC. The authors' study showed that 0.3% sodium hyaluronate pretreatment reduced the cytotoxicity of BAC in cultured corneal epithelial cells, whereas an in vivo study in mice showed that a 0.3% sodium hyaluronate instillation was suggested and that the drug may enhance the cytotoxicity of separately administered BAC. It is suggested that sodium hyaluronate prolonged the retention of BAC on the ocular surface. However, there have been no reports of this problem in the clinical setting. It is important for ophthalmologists to understand the properties of additives other than the active pharmaceutical ingredients in eyedrops.


Assuntos
Compostos de Benzalcônio/efeitos adversos , Perda de Células Endoteliais da Córnea/induzido quimicamente , Epitélio Anterior/efeitos dos fármacos , Epitélio Anterior/patologia , Soluções Oftálmicas/efeitos adversos , Conservantes Farmacêuticos/efeitos adversos , Animais , Compostos de Benzalcônio/metabolismo , Células Cultivadas , Perda de Células Endoteliais da Córnea/metabolismo , Interações Medicamentosas , Síndromes do Olho Seco/tratamento farmacológico , Epitélio Anterior/citologia , Epitélio Anterior/metabolismo , Humanos , Ácido Hialurônico/farmacologia , Camundongos
12.
Yakugaku Zasshi ; 141(1): 47-53, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33390447

RESUMO

The use of eye drops is a well-established practice in the treatment of ophthalmic diseases, although the bioavailability of traditional eye drops, which are either solutions or suspensions, is insufficient, as the corneal barrier and dilution by lacrimation prevent the transcorneal penetration of drugs. Additionally, frequent instillation may cause undesirable systemic side effects and local corneal toxicity. To overcome these problems, micro- and nanoparticles, hydrogels, and viscous solutions have been tested, and solid nanoparticles are also expected to be applied. This review examines the usefulness of ophthalmic formulations based on solid nanoparticles, by using the specific example of indomethacin (IMC). Ophthalmic formulations based on solid IMC nanoparticles (IMC-NP dispersions) have been prepared using various additives (benzalkonium chloride, mannitol, methylcellulose, and cyclodextrin) and a rotation/revolution pulverizer (NP-100), to produce particles of 50-220 nm in size. The solubility of IMC in IMC-NP dispersions was 4.18-fold higher than that in the suspensions containing IMC microparticles (IMC-MP suspensions), and IMC-NP dispersions were better tolerated than commercially available NSAIDs eye drops, such as IMC, pranoprofen, diclofenac, bromfenac, and nepafenac eyedrops, in human corneal epithelial cells. Moreover, the corneal penetration in IMC-NP dispersions was higher than that in commercially available IMC and IMC-MP suspensions, and three energy-dependent endocytosis pathways (clathrin-dependent endocytosis, caveolae-dependent endocytosis, and macropinocytosis) were related to the high ophthalmic bioavailability of IMC-NP dispersions. This information can be used to support future studies aimed at designing novel ophthalmic formulations.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Indometacina/administração & dosagem , Nanopartículas , Soluções Oftálmicas , Anti-Inflamatórios não Esteroides/farmacocinética , Disponibilidade Biológica , Desenho de Fármacos , Endocitose/fisiologia , Epitélio Anterior , Humanos , Indometacina/farmacocinética , Excipientes Farmacêuticos , Solubilidade , Suspensões
13.
Curr Opin Ophthalmol ; 32(2): 129-133, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395110

RESUMO

PURPOSE OF REVIEW: To discuss a new class of medication that has recently become available for the treatment of glaucoma; as well as share insights into developments in glaucoma medicine administration which has the potential to revolutionize medical therapy for glaucoma. RECENT FINDINGS: Newly available eye drops, netarsudil 0.02% and latanoprostene bunod 0.024%, are improving aqueous outflow through the conventional outflow tract. Other new developments in medical glaucoma are focused on alternative methods for sustained glaucoma medication delivery. SUMMARY: Newer medications may be able to extend the duration of medically controlled glaucoma, delaying or possibly eliminating the need of glaucoma surgery for some patients. Alternative methods of delivery for glaucoma medications may be a key factor in improving outcomes with currently available medications.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzoatos/uso terapêutico , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Prostaglandinas F Sintéticas/uso terapêutico , beta-Alanina/análogos & derivados , Administração Oftálmica , Humanos , Soluções Oftálmicas , beta-Alanina/uso terapêutico , Quinases Associadas a rho/antagonistas & inibidores
14.
BMC Infect Dis ; 21(1): 82, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461505

RESUMO

BACKGROUND: Keratitis due to by filamentous fungi are not easy to diagnose thus causing a delay in correct therapy. There are many descriptions of keratitis due to Candida, Fusarium and Aspergillus genera. Subramaniula genus has only recently been reported to cause human infections and there are few descriptions of eye infections due to this filamentous fungus. Diagnosis of fungal keratitis is usually based on microscopic and cultural techniques of samples obtained by corneal swabbing or scraping. Considering the amount of time required to obtain culture results it is wise to use other diagnostic methods, such as molecular analyses. Therapeutic options against these fungi are limited by low tissue penetration in the eye due to ocular barriers. We describe the first case of S. asteroides human keratitis treated with isavuconazole. CASE PRESENTATION: We describe a rare case of fungal keratitis unresponsive to antimicrobial treatment in a 65-year-old male patient without a history of diabetes or immunological diseases. He reported that the onset of symptoms occurred during a long holiday in Cape Verde Island. Initial treatment with topical antibiotics associated to steroids were ineffective, allowing a slow clinical progression of disease to corneal perforation. On admission in our Hospital, slit-lamp examination of the left eye showed conjunctival congestion and hyperemia, a large inferior corneal ulceration with brown pigment, corneal edema, about 3 mm of hypopyon and irido-lenticular synechiae. The slow clinical progression of the disease to corneal perforation and the aspect of the ulcer were consistent with a mycotic etiology. Molecular methods used on fungal colonies isolated by Sabouraud's dextrose agar cultures allowed the identification of Subramaniula asteroids from corneal scraping. Antimicrobial test showed a good susceptibility of this filamentous fungus to voriconazole and isavuconazole. Moreover, this fungal keratitis was successfully treated with isavuconazole, without side effects, observing a progressive clinical improvement. CONCLUSIONS: Molecular methods may be useful for the identification of filamentous fungal keratitis on scraping samples thus shortening the time of diagnosis. Systemic therapy by isavuconazole could be useful to treat the filamentous fungal keratitis, reducing the possible adverse effects due to the use of voriconazole by systemic administration.


Assuntos
Úlcera da Córnea/diagnóstico , Infecções Oculares Fúngicas/diagnóstico , Sordariales/isolamento & purificação , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Diagnóstico Diferencial , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Masculino , Nitrilos/administração & dosagem , Nitrilos/uso terapêutico , Soluções Oftálmicas , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Triazóis/administração & dosagem , Triazóis/uso terapêutico
15.
Am J Vet Res ; 82(1): 81-87, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33369491

RESUMO

OBJECTIVE: To investigate the effects of short-term and prolonged topical instillation of 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, and 0.03% flurbiprofen sodium on corneal sensitivity (CS) in ophthalmologically normal cats. ANIMALS: 12 healthy adult domestic shorthair cats. PROCEDURES: In the first of 2 study phases, each cat received 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, 0.03% flurbiprofen sodium, and saline (0.9% NaCl; control) solutions (1 drop [0.05 mL]/eye, q 5 min for 5 treatments) in a randomized order with a 2-day washout period between treatments. For each cat, an esthesiometer was used to measure CS before treatment initiation (baseline) and at 15, 30, 45, and 60 minutes after the last dose. There was a 2-day washout period between phases. The second phase was similar to the first, except each treatment was administered at a dosage of 1 drop/eye, twice daily for 5 days and CS was measured before treatment initiation and at 15 minutes and 24 and 48 hours after the last dose. The Friedman test was used to evaluate change in CS over time. RESULTS: None of the 4 treatments had a significant effect on CS over time in either study phase. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that neither short-term nor prolonged topical instillation of 3 NSAID ophthalmic solutions had any effect on the CS of healthy cats. Given potential differences in cyclooxygenase expression between healthy and diseased eyes, further investigation of the effects of topical NSAID instillation in the eyes of cats with ocular surface inflammation is warranted.


Assuntos
Diclofenaco , Cetorolaco de Trometamina , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides , Gatos , Flurbiprofeno , Soluções Oftálmicas
16.
Phytomedicine ; 80: 153375, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33096452

RESUMO

BACKGROUND: Dry age-related macular degeneration (dAMD) leads to serious burden of visual impairment and there is no definitive treatment. Previous studies have showed that naringenin (NAR) significantly increased electroretinography (ERG) c-wave in sodium iodate (NaIO3)-treated rats and viability of NaIO3-treated ARPE-19 cells. But the underlying mechanism is still unknown. PURPOSE: We tested the hypothesis that anti-oxidation mediated by Sirtuin 1 (SIRT1) was important to the protective effect of NAR on dAMD. STUDY DESIGN/METHODS: NaIO3-induced mice retinopathy and ARPE-19 cells injury models were established. In vivo, the protective effect of NAR eye drops on retina was evaluated by flash ERG (FERG) recording and histopathological examination. In vitro, viability of ARPE-19 cells, and the levels of lactic dehydrogenase (LDH), reactive oxygen species (ROS) and carbonyl protein were detected. Protein expression of SIRT1 was analyzed by immunochemical staining, immunofluorescence and western blotting. RESULTS: NAR eye drops improved retinal function and morphology and normalized the protein expression of SIRT1 in mice exposed to NaIO3. NAR promoted the survival of ARPE-19 cells in a concentration-dependent manner. NAR up-regulated SIRT1 protein expression, and decreased levels of ROS and carbonyl protein. Moreover, EX527, a selective inhibitor of SIRT1, abolished the effects of NAR on the cell viability and ROS. In addition, SRT1720, a selective agonist of SIRT1, improved the viability of cells and suppressed the production of ROS. CONCLUSION: Our findings indicate that SIRT1-mediated anti-oxidation contributes to the protective effect of NAR eye drops on dAMD.


Assuntos
Flavanonas/farmacologia , Substâncias Protetoras/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Carbazóis/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Iodatos/toxicidade , L-Lactato Desidrogenase/metabolismo , Masculino , Camundongos , Soluções Oftálmicas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/tratamento farmacológico , Epitélio Pigmentado da Retina/citologia , Regulação para Cima/efeitos dos fármacos
17.
Biomed Pharmacother ; 133: 111041, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378949

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1)-dependent cell death in the retinal pigment epithelium (RPE) is implicated in dry age-related macular degeneration (AMD). Although PARP1 inhibitors are available for treating dry AMD, their delivery route is not ideal for patients. The aim of this study was to test the efficacy of a novel PARP1-inhibitory compound (PIC) in vitro and in vivo. This study presents PIC, a novel small molecule, with superior efficacy to PARP1 inhibitors in the market. PIC demonstrated a distinctive inhibitory profile against PARP isotypes than the FDA-approved PARP1 inhibitors. PIC inhibited PARP1 activation at an IC50 of 0.41 ± 0.15 nM in an enzyme-based assay in vitro and at IC50 and EC50 in ARPE-19 cells of 0.11 ± 0.02 nM and 0.22 ± 0.02 nM, respectively, upon H2O2 insult. PIC also moderated mitochondrial fission and depolarization and maintained cellular energy levels under oxidative stress in ARPE-19 cells. Furthermore, PIC demonstrated good corneal penetration in a rat model, presenting PIC as a promising candidate for eye drop therapeutics for dry AMD. When PIC was administered as an eye drop formulation, RPE morphology was preserved, maintaining the thickness of the outer nuclear layers under sodium iodate (SI) treatment in rats. In SI-treated rabbits, eye drop administration of PIC also retained the structural and functional integrity when analyzed using funduscopy and electroretinogram. Collectively, our data portray PIC as an attractive treatment measure for dry AMD.


Assuntos
Degeneração Macular/tratamento farmacológico , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Administração Oftálmica , Animais , Antioxidantes/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Iodatos , Degeneração Macular/induzido quimicamente , Degeneração Macular/enzimologia , Degeneração Macular/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Absorção Ocular , Soluções Oftálmicas , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Coelhos , Ratos Sprague-Dawley , Epitélio Pigmentado da Retina/enzimologia , Epitélio Pigmentado da Retina/patologia
18.
BMC Ophthalmol ; 20(1): 489, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334316

RESUMO

BACKGROUND: Anterior uveitis secondary to topical brimonidine administration is rare and not well-defined. In glaucoma patients using brimonidine, one must consider this phenomenon to avoid mis-diagnosis and over-treatment with topical steroids which in turn may increase intraocular pressure (IOP). This is the largest case series including the longest patient follow-up in the current literature. METHODS: Sixteen patients (26 eyes) with consultant diagnosed brimonidine-associated anterior uveitis in a tertiary referral glaucoma clinic presenting between 2015 and 2019 were included in this retrospective case series. Clinical records were taken for descriptive analysis. Main outcome measures were the key clinical features, and disease course (therapy, IOP control, patient outcome). RESULTS: Key features were conjunctival ciliary injection and mutton fat keratic precipitation in all eyes. The findings were bilateral in 10 patients. Time between initiation of brimonidine treatment and presentation was 1 week to 49 months. Glaucoma sub-types were mostly pseudo-exfoliative and primary open angle glaucoma. Brimonidine treatment was stopped immediately. Additionally, topical corticosteroids were prescribed in 18 eyes and tapered down during the following 4 weeks. Thirteen eyes did not need surgical or laser treatment (median follow-up time 15 months). No patient showed recurrence of inflammation after cessation of brimonidine. CONCLUSIONS: This type of anterior uveitis is an uncommon but important manifestation which should always be considered in glaucoma patients on brimonidine treatment. Although treatable at its root cause, problems may persist, especially with respect to IOP control. The latter may necessitate glaucoma surgery after the resolved episode of the uveitis.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Tartarato de Brimonidina/efeitos adversos , Uveíte Anterior/induzido quimicamente , Administração Oftálmica , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Soluções Oftálmicas , Estudos Retrospectivos , Uveíte Anterior/diagnóstico
19.
BMJ Case Rep ; 13(12)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33318249

RESUMO

Here, we report a novel case of corneal ulcer in a 72-year-old patient with diabetes caused by Corynebacterium amycolatum This organism should not be ignored as a harmless commensal whenever it is isolated in pure form in repeat cultures of the specimen along with a leucocyte reaction in direct microscopic examination. Moreover, this organism is multidrug-resistant, so species identification of diphtheroids is important to start appropriate antibiotic therapy. There are very few published reports of ocular infection and none of corneal ulcer by this organism.


Assuntos
Úlcera da Córnea/microbiologia , Infecções por Corynebacterium/microbiologia , Corynebacterium/isolamento & purificação , Idoso , Antibacterianos/administração & dosagem , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Infecções por Corynebacterium/diagnóstico , Infecções por Corynebacterium/tratamento farmacológico , Humanos , Masculino , Soluções Oftálmicas
20.
ACS Appl Mater Interfaces ; 12(52): 57710-57720, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33320520

RESUMO

There is a continuing, urgent need for an ophthalmic (eye) drop for the clinical therapy of age-related macular degeneration (AMD), a leading cause of blindness. Here, we report the first formulation of an eye drop that is effective via autophagy for AMD treatment. This eye drop is based on a single natural product derivative (ACD), which is an amphiphilic molecule containing a 6-aminohexanoate group (H2N(CH2)5COO-). We demonstrate that this eye drop reverses the abnormal angiogenesis induced in a primate model of AMD that has the pathological characteristics close to that of human AMD. The ACD molecule was self-assembled in an aqueous environment leading to nanoparticles (NPs) about 9.0 nm in diameter. These NPs were encapsulated in calcium alginate hydrogel. The resulting eye drop effectively slowed the release of ACD and displayed extended release periods in both simulated blood (pH 7.4) and inflammatory (pH 5.2) environments. We show that the eye drop penetrated both the corneal and blood-eye barriers and reached the fundus. With low cellular toxicity, the drop targeted S1,25D3-membrane-associated rapid response steroid-binding protein (1,25D3-MARRS) promoting autophagy in a dose-dependent manner. In addition, the drop inhibited cell migration and tubular formation. On the other hand, when protein 1,25D3-MARRS was knocked down, the eye drop did not exhibit such inhibition functionalities. Our study indicates that the 6-aminohexanoate group on self-assembled NPs encapsulated in hydrogel leads to the positive in vivo outcomes. The present formulation offers a promising approach for clinical treatment of human AMD.


Assuntos
Produtos Biológicos/química , Degeneração Macular/tratamento farmacológico , Terapia de Alvo Molecular , Nanopartículas/química , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Animais , Autofagia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neovascularização de Coroide/complicações , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Macaca mulatta , Degeneração Macular/complicações , Degeneração Macular/patologia , Modelos Moleculares , Conformação Molecular , Soluções Oftálmicas/uso terapêutico
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