Mitochondria- and caspase-dependent cell death pathway involved in neuronal degeneration in diabetic retinopathy

• Published in: British journal of ophthalmology Vol. 92; no. 4; pp. 552 - 556
• Main Authors: Oshitari, T, Yamamoto, S, Hata, N, Roy, S
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01.04.2008; BMJ; BMJ Publishing Group LTD
• Subjects: Aged; bcl-2-Associated X Protein - metabolism; bcl-2-Associated X Protein - physiology; Biological and medical sciences; Caspase 3 - metabolism; Caspase 3 - physiology; Caspase 9 - metabolism; Caspase 9 - physiology; Caspases - physiology; Cell Death; Diabetes. Impaired glucose tolerance; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Diabetic Retinopathy - physiopathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Humans; Medical sciences; Middle Aged; Miscellaneous; Mitochondria - physiology; Ophthalmology; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Retinopathies; Signal Transduction; Endocrinopathy; Peptidases; Eye disease; Mitochondria; Retinopathy; Enzyme; Cell death; Diabetes mellitus; Caspase; Hydrolases; Degeneration; Ophthalmology
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjo.2007.132308

Background:Neuronal abnormalities are associated with the pathogenesis of diabetic retinopathy. However, the mechanisms for neuronal cell death in diabetic retinopathy remain unclear.Aim:To determine whether altered expression of Bax, caspase-9 and -3 is associated with degenerative neurons in diabetic retinopathy.Methods:Immunohistochemistry was performed on cryosections obtained from five pairs of normal and five pairs of age-matched diabetic human retinas. Diabetic eyes had no proliferative diabetic retinopathy and no histories of photocoagulation or ocular surgery. In this study, Fluoro-Jade B (FJB) was used as a marker for identification of degenerative neurons.Results:In diabetic retinas, Bax overexpression coexisted with FJB positive signals in the ganglion cell layer (GCL) compared with very low FJB levels in the normal retina. Increased level of the active forms of caspase-9 and -3 expressions coexisted with FJB positive cells in the GCL of diabetic retinas compared with those in normal retinas.Conclusions:Upregulation of Bax, caspase-9 and -3 expression was associated with neuronal degeneration in diabetic retinopathy. The mitochondria- and caspase-dependent cell-death pathway may be, in part, associated with neuronal degeneration in diabetic retinas.