Abstract
Purpose :
Glaucoma is a complex neurodegenerative disease that affects 80 million people world-wide. Loss of retinal ganglion cells (RGCs) and degeneration of the optic nerve are the major pathological hallmarks. We discovered recently that insulin-like growth factor binding protein like-1 (IGFBPL-1) , a member of the IGFBP superfamily proteins, promoted the regeneration of RGC axons in vitro and in vivo through binding to IGF-1. Here we examined the effect of IGFBPL1 in a mouse model of glaucoma.
Methods :
We induced elevation of intraocular pressure (IOP) by anterior chamber injection of microbeads. Mice were then divided into two groups: one group received intravitreous injections of IGFBPL-1 and the other group received saline injections on day 3, 10 and 17 after the microbead injection. Retina/RGC function and mouse visual behavior (visual acuity and contrast sensitivity) were assessed by electroretinogram (ERG) positive scotopic threshold response (pSTR) and optomotor kinetic (OMR) assay on day 0 and then every two weeks until sacrifice. Mice were sacrificed at 8 weeks post microbead injection and RGC and axon loss was quantified.
Results :
Elevated IOP induced RGC and visual function decline as measured by ERG/pSTR and OMR. Administration of IGFBPL1 significantly improved pSTR and visual behavior compared to saline-injected group. Moreover, after induce high IOP for 8 weeks, the RGCs loss rate in Saline group is 42.3±3.2%, which is 19.2±1.9% in IGFBPL-1 group.
Conclusions :
IGFBPL1 presents a strong neuroprotective effect for RGCs against glaucomatous neural damage. The finding suggests a new therapeutic strategy for RGC protection and rescuing vision in glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.