Temporal Dynamics of Mitochondrial Dysfunction and Retinal Ganglion Cell Degeneration Following Endothelin-1 Exposure
| dc.creator | Brooks, Calvin | en_US |
| dc.creator | Kodati, Bindu | en_US |
| dc.creator | Stankowska, Dorota | en_US |
| dc.creator | Krishnamoorthy, Raghu | en_US |
| dc.creator.orcid | 0000-0002-3186-0404 (Brooks, Calvin) | |
| dc.date.accessioned | 2024-04-17T12:58:10Z | |
| dc.date.available | 2024-04-17T12:58:10Z | |
| dc.date.issued | 2024-03-21 | en_US |
| dc.description.abstract | Purpose: Endothelin-1 (ET-1) and its receptors have been identified as upregulated factors in the aqueous humor and retina of animal models with glaucoma, implicating them in the pathogenesis of glaucomatous neurodegeneration. This study aims to investigate the effects of ET-1 on mitochondrial morphology, a key aspect of cellular health. Methods: C57BL/6J mice (13 weeks old) received intravitreal injections of either ET-1 or vehicle (water) in both eyes 24 hours, 72 hours, or 7 days before collection. One eye was used for retinal flat mounts stained with RBPMS to quantify retinal ganglion cells (RGCs), while the other eye was processed for transmission electron microscopy after paraffin embedding. Optic nerves were sectioned, and ten images were captured per nerve section. Mitochondria within optic nerve axons were enumerated and graded based on cristae appearance (with grades ranging from 1 to 5). Comparisons between vehicle and ET-1 treated eyes at each time point were performed for mitochondrial scores and counts (Mann-Whitney test, n=4 per group). Cell counts from retinal flat mounts were compared across groups and time points (Student’s T Test). Results: Significant RGC loss was observed in the peripheral and mid-peripheral retina 24 hours post ET-1 injection (P=0.01 and 0.04 respectively), with the disparity between vehicle and ET-1 treatments diminishing at later time points. While a trend towards reduced mitochondrial numbers in optic nerve axons post ET-1 injection was noted across all time points, significance was not reached. Mitochondrial health scores were notably diminished at 24 hours post-injection in both vehicle and ET-1 treated groups, with ET-1 demonstrating appreciable damage to mitochondria at 72 hours compared to vehicle-injected animals. However, mitochondrial health improved over time in the ET-1 treated group, with no discernible differences observed at 7 days. Conclusion: The acute decline in mitochondrial morphology following intravitreal injection of both ET-1 and vehicle suggests induced cellular stress. However, ET-1 injection led to immediate cell death not observed in the vehicle-injected cohort. While mitochondrial morphology swiftly recovered in the vehicle-injected group, ET-1 administration prolonged mitochondrial damage. These alterations in mitochondrial morphology may impair mitochondrial energy production efficiency, potentially contributing to retinal ganglion cell vulnerability in glaucoma. | en_US |
| dc.description.sponsorship | NIH EY028179, NIH T32AG020494 | en_US |
| dc.identifier.uri | https://hdl.handle.net/20.500.12503/32647 | |
| dc.language.iso | en | |
| dc.title | Temporal Dynamics of Mitochondrial Dysfunction and Retinal Ganglion Cell Degeneration Following Endothelin-1 Exposure | en_US |
| dc.type | presentation | en_US |
| dc.type.material | text | en_US |