Abstract
Purpose :
Extracellular matrix in the central nervous system comprises a complex macromolecular combination of proteins and polysaccharides that provides a substrate for maintenance of neurons and their axons. Glaucoma and other optic neuropathies involve degradation of the extracellular matrix in the retina and optic nerve head, through which unmyelinated retinal ganglion cell axons pass in forming the optic nerve proper. This degradation also affects collagen fibers, which are a major constituent of the matrix. Here we tested whether collagen mimetic peptides (CMPs), which repair damaged collagen, promote (1) survival and neurite outgrowth of neurons in vitro stressed by collagen degradation and (2) ganglion cell axon function in an inducible mouse model of glaucoma.
Methods :
For in vitro studies, we compared neurite outgrowth of dorsal root ganglion cells (DRGs) plated on partially digested type 1 collagen and treated either with CMP or vehicle. For in vivo testing of efficacy, we elevated ocular pressure unilaterally in mice using microbead occlusion and measured anterograde axonal transport of cholera toxin B to the superior colliculus following topical CMP treatment vs. vehicle.
Results :
In vitro, DRG neurons on damaged collagen treated with CMP demonstrated increased dendritic field area (p≤0.03) and neurite length (p≤0.02) compared to untreated, while neurite length in treated collagen also exceeded by 70% length in naïve collagen (p=0.002). In vivo, following three weeks of elevated ocular pressure (+35%), treatment with CMP’s significantly protected axon transport vs untreated (p<0.01).
Conclusions :
Our results emphasize the critical role intact collagen plays in maintaining ECM and neuronal function. CMPs offer therapeutic potential for use in neuroprotective or reparative regimens designed to promote neurite growth and axon function in glaucoma and other optic neuropathies
This is a 2021 ARVO Annual Meeting abstract.