| Title |
Caspase-7: a critical mediator of optic nerve injury-induced retinal ganglion cell death
|
|---|---|
| Published in |
Molecular Neurodegeneration, August 2015
|
| DOI | 10.1186/s13024-015-0039-2 |
| Pubmed ID | |
| Authors |
Shreyasi Choudhury, Yang Liu, Abbot F. Clark, Iok-Hou Pang |
| Abstract |
Axonal injury of the optic nerve (ON) is involved in various ocular diseases, such as glaucoma and traumatic optic neuropathy, which leads to apoptotic death of retinal ganglion cells (RGCs) and loss of vision. Caspases have been implicated in RGC pathogenesis. However, the role of caspase-7, a functionally unique caspase, in ON injury and RGC apoptosis has not been reported previously. The purpose of this study is to evaluate the role of caspase-7 in ON injury-induced RGC apoptosis. C57BL/6 (wildtype, WT) and caspase-7 knockout (Casp7 (-/-) ) mice were used. We show that ON crush activated caspase-7 and calpain-1, an upstream activator of caspase-7, in mouse RGCs, as well as hydrolysis of kinectin and co-chaperone P23, specific substrates of caspase-7. ON crush caused a progressive loss of RGCs to 28 days after injury. Knockout of caspase-7 partially and significantly protected against the ON injury-induced RGC loss; RGC density at 28 days post ON crush in Casp7 (-/-) mice was approximately twice of that in WT ON injured retinas. Consistent with changes in RGC counts, spectral-domain optical coherence tomography analysis revealed that ON crush significantly reduced the in vivo thickness of the ganglion cell complex layer (including ganglion cell layer, nerve fiber layer, and inner plexiform layer) in the retina. The ON crush-induced thinning of retinal layer was significantly ameliorated in Casp7 (-/-) mice when compared to WT mice. Moreover, electroretinography analysis demonstrated a decline in the positive component of scotopic threshold response amplitude in ON crushed eyes of the WT mice, whereas this RGC functional response was significantly higher in Casp7 (-/-) mice at 28 days post injury. Altogether, our findings indicate that caspase-7 plays a critical role in ON injury-induced RGC death, and inhibition of caspase-7 activity may be a novel therapeutic strategy for glaucoma and other neurodegenerative diseases of the retina. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 50 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 16% |
| Researcher | 7 | 14% |
| Student > Bachelor | 4 | 8% |
| Student > Doctoral Student | 3 | 6% |
| Student > Master | 3 | 6% |
| Other | 7 | 14% |
| Unknown | 18 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 18% |
| Neuroscience | 9 | 18% |
| Agricultural and Biological Sciences | 4 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
| Nursing and Health Professions | 2 | 4% |
| Other | 6 | 12% |
| Unknown | 17 | 34% |
Attention Score in Context
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#15,364,458
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Outputs of similar age from Molecular Neurodegeneration
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