Developmental Dynamics of Scar Formation After Optic Nerve Crush

Authors:

Elane Kim, Ryan Donahue, Zhigang He

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

Retinal ganglion cells (RGCs) are long projection neurons whose formation affect injury susceptibility. We hypothesize that the axons converge to form the optic nerve, which transmits visual extent and timing of scar formation differ across developmental information from the retina to the brain. Despite efforts to promotstages, contributing to variations in RGC resilience. neuronal survival and regeneration after axonal injury, curative To test this, we performed ONC on mice at postnatal day therapies for neuropathies like glaucoma remain lacking. Optic nerve crush (ONC) is a common model of axonal injury that 14 (P14), P26, and P42, collecting optic nerves at three and uniformly severs RGC axons, enabling in vivo testing of pro- five days post-crush. Histological and immunofluorescence analyses were applied to evaluate scar development: GFAP survival strategies. Previous work in our lab has shown that marked the glial component, Collagen I marked the fibrotic susceptibility to ONC varies throughout development: certain ages component, and Cd68 marked inflammation. By correlating demonstrate greater RGC survival and resilience, suggesting that the molecular injury response shifts dynamically over time. scar formation with differential RGC susceptibility, we aim to study how extrinsic factors contribute to age-dependent resilience. In ONC, the initial insult induces local cell death, inflammation, Understanding how glial and fibrotic responses evolve with and disruption of the blood-nerve barrier. These extrinsic age could reveal mechanisms that inform survival, alongside environmental responses can vary with age, compounding intrinsic developmental windows when therapeutic interventions could be regenerative variability. The central nervous system reacts to most effective. These findings can provide insight into ways to ONC by forming glial and fibrotic scar tissue to isolate the injurymodulate the post-injury environment, ultimately promoting repair site and restore homeostasis. Beyond RGC-intrinsic properties, in optic neuropathies. ONC offers a model to study how extrinsic programs like scar

Abstract:

Retinal ganglion cells (RGCs) are long projection neurons whose formation affect injury susceptibility. We hypothesize that the axons converge to form the optic nerve, which transmits visual extent and timing of scar formation differ across developmental information from the retina to the brain. Despite efforts to promotstages, contributing to variations in RGC resilience. neuronal survival and regeneration after axonal injury, curative To test this, we performed ONC on mice at postnatal day therapies for neuropathies like glaucoma remain lacking. Optic nerve crush (ONC) is a common model of axonal injury that 14 (P14), P26, and P42, collecting optic nerves at three and uniformly severs RGC axons, enabling in vivo testing of pro- five days post-crush. Histological and immunofluorescence analyses were applied to evaluate scar development: GFAP survival strategies. Previous work in our lab has shown that marked the glial component, Collagen I marked the fibrotic susceptibility to ONC varies throughout development: certain ages component, and Cd68 marked inflammation. By correlating demonstrate greater RGC survival and resilience, suggesting that the molecular injury response shifts dynamically over time. scar formation with differential RGC susceptibility, we aim to study how extrinsic factors contribute to age-dependent resilience. In ONC, the initial insult induces local cell death, inflammation, Understanding how glial and fibrotic responses evolve with and disruption of the blood-nerve barrier. These extrinsic age could reveal mechanisms that inform survival, alongside environmental responses can vary with age, compounding intrinsic developmental windows when therapeutic interventions could be regenerative variability. The central nervous system reacts to most effective. These findings can provide insight into ways to ONC by forming glial and fibrotic scar tissue to isolate the injurymodulate the post-injury environment, ultimately promoting repair site and restore homeostasis. Beyond RGC-intrinsic properties, in optic neuropathies. ONC offers a model to study how extrinsic programs like scar

Source:

Harvard / Wan Ting Ke, Nivedhitha Velayutham, Richard Lee / 2025

Topics:

scar, onc, optic, rgc, formation, nerve, injury, survival, developmental, susceptibility, resilience, marked

Co-authors:

@elanekim295 , @ryandonahue296 , @zhiganghe297