title: Caspase-7: a critical mediator of optic nerve injury-induced retinal ganglion cell death.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: North Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA. shreyasi83@ufl.edu.|Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA. shreyasi83@ufl.edu.|Cell Biology & Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA. shreyasi83@ufl.edu.
authors: Shreyasi
authors: S
authors: Choudhury
authors: North Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA. yang.liu@unthsc.edu.|Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA. yang.liu@unthsc.edu.
authors: Yang
authors: Y
authors: Liu
authors: North Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA. abe.clark@unthsc.edu.|Cell Biology & Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA. abe.clark@unthsc.edu.
authors: Abbot F
authors: AF
authors: Clark
authors: North Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107, USA. iok-hou.pang@unthsc.edu.|Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA. iok-hou.pang@unthsc.edu.
authors: Iok-Hou
authors: IH
authors: Pang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002154:Calpain / Q000378:metabolism; D053179:Caspase 7 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D003593:Cytoplasm / Q000201:enzymology; D004596:Electroretinography; D004789:Enzyme Activation; D004790:Enzyme Induction; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009409:Nerve Crush; D020221:Optic Nerve Injuries / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D000071876:Prostaglandin-E Synthases; D012165:Retinal Ganglion Cells / Q000201:enzymology / Q000473:pathology* / Q000502:physiology; D041623:Tomography, Optical Coherence
chemical_list: D005136:Eye Proteins; C511012:Ktn1 protein, mouse; D008565:Membrane Proteins; D002154:Calpain; C505524:Casp7 protein, mouse; D053179:Caspase 7; C112682:Capn1 protein, mouse; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases