The cold mimetic synthetic molecule zr17-2 prevents retinal lesions in a model of experimental compression of the optic nerve

CONTARTESE DS, REY-FUNES M, SOLIÑO M, FERNÁNDEZ JC, CIRANNA NS, SAROTO A, DORFMAN VB, LÓPEZ-COSTA JJ, LOIDL CF

Mar del Plata

Congreso; LXV Reunión Científica Anual. Sociedad Argentina de Investigación Clínica (SAIC); 2020

Sociedad Argentina de Investigación Clínica (SAIC)

Injuries to the optic nerve (NO) are a common damage that produces antegrade and retrograde axonal degeneration, with death of retinal ganglion cells and vision loss. Previously, we showed that ocular temperature reduction after experimental compression of NO (intraorbital optic nerve crush, IONC) significantly diminishes vision loss, and effect probably mediated by cold inducible RNA-binding proteins (CIRP). ZR17-2 is a cold mimetic synthetic molecule, able to prevent CIRP degradation in culture cells. Our aim was to evaluate the effect of ZR17-2 on retinal lesions due to NO trauma. Adult male rats (n=28) were equally distributed in groups: 1a) CTL (left eye, LE): simulation of surgery with intravitreal injection of vehicle; 1b) IONC (right eye, RE): IONC with intravitreal injection of vehicle; 2a) CTLZR (LE): simulation of surgery with intravitreal injection of ZR17-2; 2b) IONCZR (RE): IONC with intravitreal injection of ZR17-2. Each animal was its own control. Animals were euthanized five days after surgery and eyes processed for TUNEL, or placed in a dark room fifteen days after surgery for 12 hs and inspected for scotopic electroretinography (ERG) and oscillatory potentials to evaluate the integrity of the visual pathway. IONC and IONCZR depicted significant lower a- and b-waves amplitude than their respective controls; whereas, CTL and CTLZR did not show significant changes between them. In addition, IONC and IONCZR showed significant b-wave decrease related to CTL and CTLZR respectively. IONCZR showed also a significant increase in the b-wave versus IONC. Oscillatory potentials showed similar variations than ERG. On the other hand, retinas of CTL and CTLZR showed a few TUNEL+ cells, whereas IONC showed a significant increase related to CTL and IONCZR. In conclusion, the present work corroborates the effectiveness of ZR17-2 in vivo to prevent retinal lesions constituting an innovative treatment for NO trauma, and enabling it use in future preclinical trials.