title: Caspase-14: a novel caspase in the retina with a potential role in diabetic retinopathy.
abstract: OBJECTIVE
  The purpose of this study was to evaluate caspase-14 expression in the retina under normal and diabetic conditions, and to determine whether caspase-14 contributes to retinal microvascular cell death under high glucose conditions.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction and western blot analysis were used to evaluate caspase-14 expression in retinal cells, including pericytes (PCs), endothelial cells (ECs), astrocytes (ACs), choroidal ECs, and retinal pigment epithelium (RPE) cells. We also determined caspase-14 expression in the retinas of human subjects with or without diabetic retinopathy (DR) and in experimental diabetic mice. Retinal ECs and PCs were infected with adenoviruses expressing human caspase-14 or green fluorescent protein. Caspase-14 expression was also assessed in retinal vascular cells cultured under high glucose conditions. The number of apoptotic cells was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling staining and confirmed by determining the levels of cleaved poly (ADP-ribose) polymerase-1 and caspase-3.
  
  
  RESULTS
  Our experiments demonstrated that retinal ECs, PCs, ACs, choroidal ECs, and RPE cells expressed caspase-14, and DR was associated with upregulation and/or activation of caspase-14 particularly in retinal vasculature. High glucose induced marked elevation of the caspase-14 level in retinal vascular cells. There was a significant increase in the apoptosis rate and the levels of cleaved poly (ADP-ribose) polymerase-1 and caspase-3 in retinal ECs and PCs overexpressing caspase-14.
  
  
  CONCLUSIONS
  Our findings indicate that caspase-14 might play a significant role in the pathogenesis of DR by accelerating retinal PC and EC death. Further investigations are required to elaborate the underlying mechanisms.
authors.affiliation: Department of Oral Biology and Anatomy, Georgia Health Sciences University (GHSU), College of Dental Medicine, Augusta, GA 30912, USA. malshabrawey@georgiahealth.edu
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Shabrawey
authors.forename: Saif
authors.initials: S
authors.lastname: Ahmad
authors.forename: Sylvia
authors.initials: S
authors.lastname: Megyerdi
authors.forename: Amira
authors.initials: A
authors.lastname: Othman
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Palenski
authors.forename: Eui Seok
authors.initials: ES
authors.lastname: Shin
authors.forename: Zafer
authors.initials: Z
authors.lastname: Gurel
authors.forename: Stephen
authors.initials: S
authors.lastname: Hsu
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053456:Caspase 14 / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002829:Choroid / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053456:Caspase 14; D053148:Caspase 3; D005947:Glucose