000069951 001__ 69951
000069951 005__ 20190709135539.0
000069951 0247_ $$2doi$$a10.1371/journal.pone.0177998
000069951 0248_ $$2sideral$$a105105
000069951 037__ $$aART-2017-105105
000069951 041__ $$aeng
000069951 100__ $$aFernandez-Sanchez, L.
000069951 245__ $$aControlled delivery of tauroursodeoxycholic acid from biodegradable microspheres slows retinal degeneration and vision loss in P23H rats
000069951 260__ $$c2017
000069951 5060_ $$aAccess copy available to the general public$$fUnrestricted
000069951 5203_ $$aSuccessful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D, L-lactic-co-glycolic acid) (PLGA) microspheres for the treatment of the retina in a rat model of retinitis pigmentosa. PLGA microspheres (MSs) containing TUDCA were produced by the O/W emulsion-solvent evaporation technique. Particle size and morphology were assessed by light scattering and scanning electronic microscopy, respectively. Homozygous P23H line 3 rats received a treatment of intravitreal injections of TUDCA-PLGA MSs. Retinal function was assessed by electroretinography at P30, P60, P90 and P120. The density, structure and synaptic contacts of retinal neurons were analyzed using immunofluorescence and confocal microscopy at P90 and P120. TUDCA-loaded PLGA MSs were spherical, with a smooth surface. The production yield was 78%, the MSs mean particle size was 23 mu m and the drug loading resulted 12.5 +/- 0.8 mu g TUDCA/mg MSs. MSs were able to deliver the loaded active compound in a gradual and progressive manner over the 28-day in vitro release study. Scotopic electroretinografic responses showed increased ERG a- and b-wave amplitudes in TUDCA-PLGA-MSstreated eyes as compared to those injected with unloaded PLGA particles.TUDCA-PLGAMSs- treated eyes showed more photoreceptor rows than controls. The synaptic contacts of photoreceptors with bipolar and horizontal cells were also preserved in P23H rats treated with TUDCA-PLGA MSs. This work indicates that the slow and continuous delivery of TUDCA from PLGA-MSs has potential neuroprotective effects that could constitute a suitable therapy to prevent neurodegeneration and visual loss in retinitis pigmentosa.
000069951 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/RETICS-FEDER-RD16-0008-0009$$9info:eu-repo/grantAgreement/ES/ISCIII/RETICS-FEDER-RD16-0008-0016$$9info:eu-repo/grantAgreement/ES/MICINN-FEDER/MAT2013-43127R$$9info:eu-repo/grantAgreement/ES/MINECO-FEDER/BFU2015-67139-R
000069951 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000069951 590__ $$a2.766$$b2017
000069951 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 64 = 0.234$$c2017$$dQ1$$eT1
000069951 592__ $$a1.164$$b2017
000069951 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2017$$dQ1
000069951 593__ $$aMedicine (miscellaneous)$$c2017$$dQ1
000069951 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2017$$dQ1
000069951 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000069951 700__ $$aBravo-Osuna, I.
000069951 700__ $$aLax, P.
000069951 700__ $$aArranz-Romera, A.
000069951 700__ $$aManeu, V.
000069951 700__ $$aEsteban-Perez, S.
000069951 700__ $$0(orcid)0000-0003-0349-9997$$aPinilla, I.$$uUniversidad de Zaragoza
000069951 700__ $$aPuebla-Gonzalez, M.D.
000069951 700__ $$aHerrero-Vanrell, R.
000069951 700__ $$aCuenca, N.
000069951 7102_ $$11004$$2646$$aUniversidad de Zaragoza$$bDpto. Cirugía,Ginecol.Obstetr.$$cÁrea Oftalmología
000069951 773__ $$g12, 5 (2017), e0177998[20 pp]$$pPLoS One$$tPloS one$$x1932-6203
000069951 8564_ $$s1393849$$uhttps://zaguan.unizar.es/record/69951/files/texto_completo.pdf$$yVersión publicada
000069951 8564_ $$s112004$$uhttps://zaguan.unizar.es/record/69951/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000069951 909CO $$ooai:zaguan.unizar.es:69951$$particulos$$pdriver
000069951 951__ $$a2019-07-09-12:06:29
000069951 980__ $$aARTICLE