AI Article Synopsis

  • Optic neuropathies, particularly glaucoma, lead to significant vision loss by damaging retinal ganglion cell (RGC) axons in response to increased intraocular pressure (IOP), with current treatments primarily aimed at lowering IOP.
  • Research explored collagen mimetic peptides (CMPs) as a potential new therapy, showing that CMPs enhanced neurite outgrowth and improved axon transport in mouse models with elevated IOP.
  • The findings indicate that CMPs could serve as a promising neuroprotective treatment for glaucoma patients, particularly those who do not benefit from traditional IOP-lowering therapies.

Article Abstract

Optic neuropathies are a major cause of visual disabilities worldwide, causing irreversible vision loss through the degeneration of retinal ganglion cell (RGC) axons, which comprise the optic nerve. Chief among these is glaucoma, in which sensitivity to intraocular pressure (IOP) leads to RGC axon dysfunction followed by outright degeneration of the optic projection. Current treatments focus entirely on lowering IOP through topical hypotensive drugs, surgery to facilitate aqueous fluid outflow, or both. Despite this investment in time and resources, many patients continue to lose vision, underscoring the need for new therapeutics that target neurodegeneration directly. One element of progression in glaucoma involves matrix metalloproteinase (MMP) remodeling of the collagen-rich extracellular milieu of RGC axons as they exit the retina through the optic nerve head. Thus, we investigated the ability of collagen mimetic peptides (CMPs) representing various single strand fractions of triple helix human type I collagen to protect RGC axons in an inducible model of glaucoma. First, using dorsal root ganglia maintained on human type I collagen, we found that multiple CMPs significantly promote neurite outgrowth (+35%) compared to vehicle following MMP-induced fragmentation of the 1(I) and 2(I) chains. We then applied CMP to adult mouse eyes following microbead occlusion to elevate IOP and determined its influence on anterograde axon transport to the superior colliculus, the primary RGC projection target in rodents. In glaucoma models, sensitivity to IOP causes early degradation in axon function, including anterograde transport from retina to central brain targets. We found that CMP treatment rescued anterograde transport following a 3-week +50% elevation in IOP. These results suggest that CMPs generally may represent a novel therapeutic to supplement existing treatments or as a neuroprotective option for patients who do not respond to IOP-lowering regimens.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592892PMC
http://dx.doi.org/10.3389/fphar.2021.764709DOI Listing

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