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Rocio Herrero-Vanrell, Laura Fernández-Sánchez, María del Mar Puebla-González, Pedro Lax, Irene Bravo-Osuna, Nicolás Cuenca; Encapsulated Tudca Plga Microspheres For The Treatment Of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3251.
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Systemic high dose of Tauroursodeoxycholic Acid (TUDCA) prevents the degeneration of photoreceptors in rd10 mice and P23H rat retina. The aim of this work was to study the use of intravitreal injection of TUDCA encapsulated in PLGA microspheres for the treatment of the P23H rat retina.
TUDCA (Calbiochem®) and PLGA (Resomer RG® 503, Boehringer Ingelheim S. A.). Microspheres (MSs) were prepared by the O/W emulsion-solvent evaporation method with a TUDCA:PLGA ratio of 2:10. Morphological and particle size characterization were performed by scanning electronic microscopy (SEM) and light scattering, respectively. Homozygous P23H line 3 rats (20 days old) were intravitreal injected with 5 µl of a suspension of TUDCA-PLGA microspheres in PBS (5% w/v) in the right eyes, and PBS in the left ones. Retinal function was assessed by electroretinogram at P80, P100 and P120. Scotopic a- and b-wave amplitudes were analyzed and differences compared by a paired Student’s t-test.
TUDCA-loaded PLGA MSs (20µg TUDCA/mg MSs) were spherical, with a smooth surface. The production yield was 55% and the MSs size distribution 2-40µm. Scotopic light-induced retinal responses registered at P80 showed a- and b- wave mean amplitudes significantly higher in TUDCA-injected eyes compared with vehicle-injected (p<0.05 and p<0.005, respectively; paired t-test). Maximal differences were observed at the maximal amplitude responses both in a- and b-waves. Significant differences in a- and b-wave amplitudes were not found at P100 and P120. Repeated injections might be necessary to reach the TUDCA level enough to produce a sustained retinal preservation.
This work suggests that encapsulated TUDCA in PLGA MSs has a potential neuroprotective effect that could be useful to delay vision loss in retinitis pigmentosa.
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