Abstract
Purpose: :
To determine whether altered expression of Bax, caspase-3 and caspase-9 are associated with degenerative neurons in diabetic retinopathy.
Methods: :
Immunohistochemistry for Bax, caspase-3, and caspase-9 was performed on serial cryosections obtained from five pairs of normal and five pairs of diabetic human retinas. Diabetic eyes used in this study had neither any history of proliferative diabetic retinopathy nor any history 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 co-existed with FJB positive signals in the ganglion cell layer (GCL) compared to very low FJB levels in the normal retina (0.71 ± 0.21% versus 0.43 ± 0.56%; P = 0.0149). The number of FJB positive cells in the GCL of diabetic retinas was significantly increased compared to those in normal retinas (0.78 ± 0.50% versus 0.34 ± 0.37%; P < 0.0001). The number of positive cells that showed active forms of caspase-3 and caspase-9 and co-existed with FJB positive signals was also significantly increased in the GCL of diabetic retinas compared to those in normal retinas (0.90 ± 0.66% versus 0.31 ± 0.25%, P = 0.007; 0.68 ± 0.39% versus 0.29 ± 0.27%, P = 0.02, respectively).
Conclusions: :
These results indicate that upregulation of Bax, caspase-3 and caspase-9 expression underlies neuronal degeneration in diabetic retinopathy. The mitochondria- and caspase-dependent cell death pathways are, at least in part, associated with neuronal degeneration in diabetic retinas.
Keywords: diabetic retinopathy • apoptosis/cell death • retina