Caspase-14: A novel caspase in the retina with a potential role in diabetic retinopathy

Mohamed Al-Shabrawey, Saif Ahmad, Sylvia Megyerdi, Amira Othman, Babak Baban, Tammy L. Palenski, Eui Seok Shin, Zafer Gurel, Stephen Hsu, Nader Sheibani

Research output: Contribution to journalArticle

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Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)1895-1906
Number of pages12
JournalMolecular Vision
Volume18
StatePublished - Sep 11 2012

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Caspase 14
Diabetic Retinopathy
Caspases
Retina
Pericytes
Endothelial Cells
Retinal Vessels
Retinal Pigment Epithelium
Glucose
Caspase 3
Astrocytes
Cell Death
Human Adenoviruses
DNA Nucleotidylexotransferase
Green Fluorescent Proteins

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Al-Shabrawey, M., Ahmad, S., Megyerdi, S., Othman, A., Baban, B., Palenski, T. L., ... Sheibani, N. (2012). Caspase-14: A novel caspase in the retina with a potential role in diabetic retinopathy. Molecular Vision, 18, 1895-1906.

Caspase-14 : A novel caspase in the retina with a potential role in diabetic retinopathy. / Al-Shabrawey, Mohamed; Ahmad, Saif; Megyerdi, Sylvia; Othman, Amira; Baban, Babak; Palenski, Tammy L.; Shin, Eui Seok; Gurel, Zafer; Hsu, Stephen; Sheibani, Nader.

In: Molecular Vision, Vol. 18, 11.09.2012, p. 1895-1906.

Research output: Contribution to journalArticle

Al-Shabrawey, M, Ahmad, S, Megyerdi, S, Othman, A, Baban, B, Palenski, TL, Shin, ES, Gurel, Z, Hsu, S & Sheibani, N 2012, 'Caspase-14: A novel caspase in the retina with a potential role in diabetic retinopathy', Molecular Vision, vol. 18, pp. 1895-1906.
Al-Shabrawey, Mohamed ; Ahmad, Saif ; Megyerdi, Sylvia ; Othman, Amira ; Baban, Babak ; Palenski, Tammy L. ; Shin, Eui Seok ; Gurel, Zafer ; Hsu, Stephen ; Sheibani, Nader. / Caspase-14 : A novel caspase in the retina with a potential role in diabetic retinopathy. In: Molecular Vision. 2012 ; Vol. 18. pp. 1895-1906.
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AU - Baban, Babak

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