IN A MOUSE MODEL OF RETINITIS PIGMENTOSA NEURONAL DEATH RESULTS FROM TRKC.T1?DEPENDENT ERK ACTIVATION UPREGULATING TNF-Α PRODUCTION IN RETINAL GLIA

ALBA GALAN; SEAN JMAEFF; PABLO F BARCELONA; SARUNIC MV; H. URI SARAGOVI

CELL DEATH AND DIFFERENTIATION

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2017

1350-9047

etinitis pigmentosa (RP) is an inherited degenerative retinal disease characterized by a progressive loss of photoreceptor that eventually culminates in irreversible blindness. Yet, the molecular mechanisms that lead to photoreceptor death have not been fully elucidated. Imbalance between full-length and truncated isoforms of Trk receptors are known to induce neuronal cell death. Here, we sought to determine whether the truncated isoform of the TrkC neurotrophin receptor, TrkC.T1, is relevant to the degeneration of photoreceptors during RP and investigate the intracellular signaling mechanisms underlying photoreceptor loss.A genetic model of engineered mice lacking TrkC.T1 crossed with a Rhodopsin mutant (RHOP347S) mouse model of RP was used to examine the effect of TrkC.T1 on the degeneration of the outer nuclear layer (ONL) and photoreceptor cell death. In RHOP:TrkC.T1+/+ mice, TrkC.T1 was up-regulated in the retinal cell layers where Müller glial cells are located. RHOP:TrkC.T1+/+