P75NTR ANTAGONISTS ATTENUATE PHOTORECEPTOR CELL LOSS IN MURINE MODELS OF RETINITIS PIGMENTOSA

MARÍA PLATÓN-CORCHADO; PABLO F BARCELONA; SEAN JMAEFF; MIGUEL MARCHENA; ALBERTO M HERNÁNDEZ-PINTO; CATALINA HERNÁNDEZ-SÁNCHEZ; H. URI SARAGOVI

CELL DEATH AND DIFFERENTIATION

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2017

1350-9047

roNGF signaling through p75NTR has been associated with neurodegenerative disorders. Retinitis pigmentosa (RP) comprises agroup of inherited retinal dystrophies that causes progressive photoreceptor cell degeneration and death, at a rate dependent onthe genetic mutation. There are more than 300 mutations causing RP, and this is a challenge to therapy. Our study was designed toexplore a common mechanism for p75NTR in the progression of RP, and assess its potential value as a therapeutic target. TheproNGF/p75NTR system is present in the dystrophic retina of the rd10 RP mouse model. Compared with wild-type (WT) retina, thelevels of unprocessed proNGF were increased in the rd10 retina at early degenerative stages, before the peak of photoreceptor celldeath. Conversely, processed NGF levels were similar in rd10 and WTretinas. ProNGF remained elevated throughout the period ofphotoreceptor cell loss, correlating with increased expression of α2-macroglobulin, an inhibitor of proNGF proce