RESUMO
Retinal degenerative diseases can have many possible causes and are currently difficult to treat. As an alternative to therapies that require genetic manipulation or the implantation of electronic devices, photopharmacology has emerged as a viable approach to restore visual responses. Here, we present a new photopharmacological strategy that relies on a photoswitchable excitatory amino acid, ATA. This freely diffusible molecule selectively activates AMPA receptors in a light-dependent fashion. It primarily acts on amacrine and retinal ganglion cells, although a minor effect on bipolar cells has been observed. As such, it complements previous pharmacological approaches based on photochromic channel blockers and increases the potential of photopharmacology in vision restoration.
Assuntos
Cegueira/tratamento farmacológico , Luz , Receptores de AMPA/metabolismo , Receptores de Ácido Caínico/metabolismo , Células Ganglionares da Retina/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Animais Recém-Nascidos , Cegueira/genética , Cegueira/patologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/deficiência , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Modelos Animais de Doenças , GABAérgicos/farmacologia , Células HEK293 , Hipocampo/citologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ácidos Fosfínicos/farmacologia , Picrotoxina/análogos & derivados , Picrotoxina/farmacologia , Piridinas/farmacologia , Receptores de Ácido Caínico/genética , Células Ganglionares da Retina/efeitos dos fármacos , Opsinas de Bastonetes/deficiência , Opsinas de Bastonetes/genética , Sesterterpenos , Proteínas rho de Ligação ao GTP/deficiência , Proteínas rho de Ligação ao GTP/genética , Receptor de GluK2 CainatoRESUMO
We studied the adsorption behavior and surface chemistry of the tobacco mosaic virus (TMV) on well-defined metal and insulator surfaces. TMV serves as a tubular supramolecular model system with precisely known surface termination. We show that if the surface chemistry of the substrate and the pH-dependent chemistry of the molecular surface match, for example, by hydrogen bonding, a strong adsorption occurs, and lateral movement is impeded. Due to the immobilization, the virion can be imaged by atomic force microscopy (AFM) in contact mode. We also used self-assembled monolayers with an acyl chloride group to induce covalent bonding via ester formation. Noncontact AFM proved that TMV keeps its cylindrical cross section only under weak adsorption conditions, that is, on hydrophobic surfaces, while on hydrophilic substrates a deformation occurs to maximize the number of interacting chemical groups.
