Mitochondria- and caspase-dependent cell death pathway involved in neuronal degeneration in diabetic retinopathy.
BACKGROUND
Neuronal abnormalities are associated with the pathogenesis of diabetic retinopathy. However, the mechanisms for neuronal cell death in diabetic retinopathy remain unclear.


OBJECTIVE
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.
Oshitari
T
T
Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Chiba, Japan. tarii@aol.com
Yamamoto
S
S
Hata
N
N
Roy
S
S
D000368:Aged; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology; D053453:Caspase 9 / Q000378:metabolism / Q000502:physiology; D020169:Caspases / Q000502:physiology*; D016923:Cell Death; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism / Q000502:physiology
C494826:BAX protein, human; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases