Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0314719 (dry eye)
 2,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LFA-1/ICAM-1 interaction is essential in support of inflammatory and specific T-cell regulated immune responses by mediating cell adhesion, leukocyte extravasation, migration, antigen presentation, formation of immunological synapse, and augmentation of T-cell receptor signaling. The increase of ICAM-1 expression levels in conjunctival epithelial cells and acinar cells was observed in animal models and patients diagnosed with dry eye. Therefore, it has been hypothesized that small molecule LFA-1/ICAM-1 antagonists could be an effective topical treatment for dry eye. In this letter, we describe the discovery of a potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonist (SAR 1118) and its development as an ophthalmic solution for treating dry eye.
ACS Med Chem Lett 2012 Mar 08
PMID:Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye. 2490 Apr 56

The optimal frequency (OF) of a biomarker in electrochemical impedance spectroscopy (EIS) is the frequency at which the EIS response best reflects the binding of the biomarker to its molecular recognition element. Commonly, biosensors rely on complicated immobilization chemistry to attach biological molecules to the sensor surface, making the direct study of a biomarker's native OF a challenge. Physical adsorption presents a simple immobilization strategy to study the native biomarker's OF, but its utility is often discouraged due to a loss in biological activity. To directly study a biomarker's native OF and investigate the potential of OF to overcome the limitations of physical adsorption, a combination of EIS and glutaraldehyde-mediated physical adsorption was explored. The experimental sensing platform was prepared by immobilizing either anti-lactoferrin (Lfn) IgG or anti-immunoglobulin E (IgE) onto screen printed carbon electrodes. After characterizing the native OFs of both biomarkers, investigation of the platform's specificity, stability, and performance in complex medium was found to be sufficient. Finally, a paper-based tear sampling component was integrated to transform the testing platform into a prototypical point-of-care dry eye diagnostic. The investigation of native OFs revealed a correlation between the native OFs (57.44 and 371.1 Hz for Lfn and IgE, respectively) and the molecular weight of the antibody-antigen complex. Impedance responses at the native OFs have enabled detection limits of 0.05 mg/mL and 40 ng/mL for Lfn and IgE, respectively, covering the clinically relevant ranges. The native OFs were found to be robust across various testing mediums and conditions.
ACS Sens 2018 04 27
PMID:Direct Measurement of a Biomarker's Native Optimal Frequency with Physical Adsorption Based Immobilization. 2953 5

The dependence of the localized surface plasmon resonance (LSPR) of noble-metal nanomaterials on refractive index makes LSPR a useful, label-free signal transduction strategy for biosensing. In particular, by decorating gold nanomaterials with molecular recognition agents, analytes of interest can be trapped near the surface, resulting in an increased refractive index surrounding the nanomaterial, and, consequently, a red shift in the LSPR wavelength. Ionic poly( N-isopropylacrylamide- co-methacrylic acid) (PNM) hydrogels were used as protein receptors because PNM nanogels exhibit a large increase in refractive index upon protein binding. Specifically, PNM hydrogels were synthesized on the surface of silica gold nanoshells (AuNSs). This composite material (AuNS@PNM) was used to detect changes in the concentration of two protein biomarkers of chronic dry eye: lysozyme and lactoferrin. Both of these proteins have high isoelectric points, resulting in electrostatic attraction between the negatively charged PNM hydrogels and positively charged proteins. Upon binding lysozyme or lactoferrin, AuNS@PNM exhibits large, concentration-dependent red shifts in LSPR wavelength, which enabled the detection of clinically relevant concentration changes of both biomarkers in human tears. The LSPR-based biosensor described herein has potential utility as an affordable screening tool for chronic dry eye and associated conditions.
ACS Nano 2018 09 25
PMID:Label-Free Detection of Tear Biomarkers Using Hydrogel-Coated Gold Nanoshells in a Localized Surface Plasmon Resonance-Based Biosensor. 3020 12

The sealed anatomical features of the eye and its physiological activity that rapidly removes drugs are called anatomical and physiological barriers, which are the cause of more than 90% of drug loss. This aspect remains a critical issue in eye surface medication. Thus, promoting tissue permeability of drugs as well as prolonging their retention on the eye surface can improve their bioavailability and enhance their therapeutic effects. Thanks to the existence of a negatively charged mucin layer on the eye surface, several peptide-decorated polymeric micelles were prepared to enhance the interaction between the micelle and eye surface, thus prolonging the drug retention on the eye surface and promoting its tissue permeability. Tacrolimus (also known as FK506) is a hydrophobic macrolide immunosuppressant used to treat dry eye syndrome and other eye diseases. However, its hydrophobic nature makes its delivery as a topical eye surface medication difficult, with the risk of side effects due to overdoses. Therefore, the aim of this work is to evaluate the ability of FK506 micelles in promoting their permeability on the eye surface. Our results showed that the positively charged nanomicelles could significantly prolong FK506 retention on the eye surface and enhance its corneal permeability in ex vivo and in vivo conditions. FK506 nanomicelles exhibited superior curing effects against dry eye diseases than the FK506 suspension and a commercial FK506 formula. It exerted better inhibitory effects on eye surface inflammation and corneal epithelium apoptosis when examined by a slip lamp and a transferase-mediated dUTP nick end labeling assay, respectively. Further assays revealed the higher suppressive effects on the expression of several inflammation-related factors at an mRNA and protein level. Hence, our results suggested that these positively charged nanomicelles might be a good drug delivery system for ocular surface medication.
ACS Appl Mater Interfaces 2019 Oct 30
PMID:Overcoming the Anatomical and Physiological Barriers in Topical Eye Surface Medication Using a Peptide-Decorated Polymeric Micelle. 3158 53