Apoptotic Retinal Ganglion Cell Death After Optic Nerve Transection or Crush in Mice: Delayed RGC Loss With BDNF or a Caspase 3 Inhibitor
| Autor: | Francisco M. Nadal-Nicolás, Marta Agudo-Barriuso, Manuel Vidal-Sanz, Francisco J. Valiente-Soriano, M.C. Sánchez-Migallón |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Retinal Ganglion Cells genetic structures Cell Survival medicine.medical_treatment Caspase 3 Apoptosis Biology Cysteine Proteinase Inhibitors Neuroprotection Andrology 03 medical and health sciences Mice 0302 clinical medicine Neurotrophic factors medicine Animals Brain-derived neurotrophic factor Retina Brain-Derived Neurotrophic Factor Optic Nerve Anatomy eye diseases Disease Models Animal 030104 developmental biology medicine.anatomical_structure Retinal ganglion cell Optic Nerve Injuries Optic nerve sense organs Axotomy Oligopeptides 030217 neurology & neurosurgery |
| Zdroj: | Investigative ophthalmologyvisual science. 57(1) |
| ISSN: | 1552-5783 |
| Popis: | Purpose To investigate retinal ganglion cell (RGC) survival and activation of caspase 3 after optic nerve crush (ONC) or transection (ONT) and treatment with brain-derived neurotrophic factor (BDNF) or Z-DEVD_fmk. Methods In albino Swiss mice, the left optic nerve was severed or crushed at 0.5 mm from the optic head and retinas were analyzed from 1 to 10 days. Additional groups were treated intravitreally with a single injection of BDNF (2.5 μg) or Z-DEVD_fmk (125 ng) right after injury, or with Z-DEVD_fmk at day 2, or with multiple injections of Z-DEVD_fmk. As controls intact or vehicle-treated retinas were used. In all retinas, Brn3a (RGCs) and cleaved-caspase 3 (c-casp3) were immunodetected and their numbers quantified. In an additional group, c-casp3 expression was assessed in RGCs retrogradely labeled before axotomy. Results The temporal loss of RGCs was the same after ONC or ONT and occurred in two phases with 65% loss during the first 7 days and an additional 4% loss from day 7 to 10. The appearance of c-casp3+RGCs is Gaussian, peaking at 4 days and declining thereafter. Brn3a down-regulates when RGCs start expressing c-casp3. Retinal ganglion cell rescue rate for BDNF or Z-DEVD_fmk is similar and both delay RGC loss by 1 day. Delayed treatment with Z-DEVD_fmk does not rescue RGCs, and several injections are not better than a single one at the time of the injury. Conclusions Brn3a down-regulation marks the beginning of RGC death, which after axotomy occurs by caspase-dependent apoptosis in at least half of the RGCs. These data should be considered when designing neuroprotective strategies. |
| Databáze: | OpenAIRE |
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