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| Titel: |
Caspase-3 inhibitor Z-DEVD-FMK enhances retinal ganglion cell survival and vision restoration after rabbit traumatic optic nerve injury |
| Auteur: |
Liu, Yuanyuan Yan, Hua Chen, Song Sabel, Bernhard A. |
| Verschenen in: |
Restorative neurology and neuroscience |
| Paginering: | Jaargang 33 (2015) nr. 2 pagina's 205-220 |
| Jaar: |
2015-01-07 |
| Inhoud: |
Purpose: Vision loss after traumatic optic nerve injury is considered irreversible because of the retrograde loss of retinal ganglion cells (RGCs) which undergo apoptosis. Because the second messenger caspase-3 plays a major role in apoptosis, we now evaluated the efficacy of the specific caspase-3 inhibitor, Z-DEVD-FMK, in a rabbit model of fluid percussion injury (FPI) which mimics traumatic optic nerve injury in humans to enhance cell survival and improve vision. Methods: Survival of RGCs and recovery of vision were studied using retinal morphological markers and visual evoked potentials (VEP), respectively. The FPI traumatized animals were treated in their right eye with a single intravitreal or peribulbar injection of Z-DEVD-FMK 30 min post-injury compared to 2% DMSO control injections in their left eye. Results: Intravitreal Z-DEVD-FMK, but not control injections, led to down-regulation of capase-3 and reduced, in a dose-dependent manner, RGCs apoptosis from 7 to 21 days post-injury. These morphological improvements were accompanied by vision restoration as documented by VEP. The neuroprotection after intravitreal injection of Z-DEVD-FMK was more effective than the peribulbar application. Conclusions: The caspase-3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when injected 30 min after optic nerve damage and significantly promotes restoration of vision. A controlled clinical trial is now needed to evaluate the efficacy and safety of Z-DEVD-FMK in humans. |
| Uitgever: |
IOS Press |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
Details van artikel 3 van 12 gevonden artikelen
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