High glucose induces caspase-independent cell death in retinal neural cells

Neurobiology of Disease

A.J. Cristóvão¹  C.M. Carvalho²  A.R. Santiago³  A.F. Ambrósio³  P.F. Santos³ 

[1] Center of Ophthalmology of Coimbra, Institute of Biomedical Research on Light and Image (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal;Center for Neuroscience and Cell Biology, Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal;

关键词: Apoptosis;    Mitochondria;    Retinopathy;    Apoptosis-inducing factor (AIF);    Diabetes;   

DOI  :  

来源: DOAJ

【 摘 要 】

Diabetic retinopathy is a leading cause of blindness among adults in the western countries. It has been reported that neurodegeneration may occur in diabetic retinas, but the mechanisms underlying retinal cell death are poorly understood. We found that high glucose increased the number of cells with condensed nuclei and the number of TUNEL-positive cells, and caused an increase in the translocation of phosphatidylserine to the outer leaflet of the plasma membrane, indicating that high glucose induces apoptosis in cultured retinal neural cells. The activity of caspases did not increase in high glucose-treated cells, but apoptosis-inducing factor (AIF) levels decreased in the mitochondria and increased in the nucleus, indicating a translocation to the nucleus where it may cause DNA fragmentation. These results demonstrate that elevated glucose induces apoptosis in cultured retinal neural cells. The increase in apoptosis is not dependent on caspase activation, but is mediated through AIF release from the mitochondria.

【 授权许可】

Unknown