Gene expression profile in retinal excitotoxicity induced by L-glutamate in neonatal rats

Abstract

In neonatal rats, glutamate could induce retinal thinning depending on the development stage, and the severity peaked at treatment on postnatal day (PND) 8. To elucidate the molecular mechanism of retinal thinning induced by L-glutamate in neonatal rats, we investigated the time-course gene expression profile in the developing retina in addition to initial histopathological changes. Histopathologically, apoptotic cells in the inner retina were observed at 6 hours after treatment on PNDs 4, 6 and 8, and inflammatory cell infiltration was noted at 24 hours. Comprehensive gene expression analysis conducted on PNDs 4 and 8 indicated that cell death/proliferation- and inflammation-related genes were upregulated and that neuron development- and neurotransmitter-related genes were downregulated. Furthermore, quantitative RT-PCR analysis of apoptosis- and inflammation-related genes performed on PNDs 4, 6, 8, 10 and 12 showed that the time-course changes of the gene expression ratios of Gadd45b and Ccl3 seemed to be related to histopathological changes of the retina induced by L-glutamate. These results revealed that the association of initial histopathological changes with the gene expression profile in the retina induced by L-glutamate and that Gadd45b and Ccl3 are considered to participate in retinal thinning induced by L-glutamate in neonatal rats.