Abstract
Purpose :
Lyve-1 is a representative lymphatic protein which mediates the transmigration of immune cells. In this study, we aimed to investigate the expression and function of lyve-1 in the optic nerve of experimental autoimmune encephalitis (EAE), an animal model of demyelinating optic neuropathy.
Methods :
We immunostained the optic nerve of acute and recovery phase EAE mice with antisera against lyve-1, MBP, neurofilament, and GFAP to determine phase dependent expression of lyve-1 in the each cellular components of the optic nerve. We also immunostained the optic nerve with neutrophil (Ly-6G) and macrophage (F4/80) markers to time dependent infiltration of immune cells into demyelinated optic nerve. To delineate the function of lyve-1, we injected neutrophil blocking antibody into peritoneal cavity of subacute phase EAE mice and then evaluated clinical score and the degree of neutrophil infiltration into optic nerve of EAE mice. To selectively suppress the axonal expression of lyve-1, we injected lyve-1 siRNA into the vitreal cavity of subacute phase EAE and determined the change in axonal damage.
Results :
In the optic nerve of acute phase EAE mice, the axon of retinal ganglion cells expresses lyve-1. Axonal lyve-1 expression shows a close spatial correlation with neutrophil infiltration. Systemic administration of lyve-1 blocking antibody improved the clinical score in the EAE mice. Intravitreal delivery of lyve-1 siRNA effectively suppressed axonal lyve-1 expression and neutrophil infiltration into the optic nerve of acute phase EAE mice. Furthermore, axonal knock-down of lyve-1 also prevented axonal loss in the optic nerve of chronic phase EAE mice.
Conclusions :
Lyve-1 is expressed in the optic nerve (especially in the axon of retinal ganglion cell) of acute phase EAE mice and it seems to mediate neutrophil infiltration into demyelinated optic nerve. By blocking the function of lyve-1, we could prevent neutrophil infiltration, axonal damage and subsequent neurological deficit in EAE mice.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.