rd1 Photoreceptor Degeneration: Photoreceptor Rescue and Role of Metalloproteases in Retinal Degeneration Ahuja Jensen, Poonam

Currently much attention is focused on glutathione S transferase (GST)-induced suppression of apoptosis. The objective of our studies was therefore to see if GST isoenzymes rescue photoreceptors in retinal explants from rd1/rd1 mice, in which photoreceptors degenerate rapidly. Eyes from C3H rd1/rd1 and / mice were collected at various time points between postnatal day (PN) 2 and PN28. Localization and content of -GST and -GST was investigated by immunofluorescence and semi-quantitative Western blot analysis, respectively. In addition, PN2 and PN7 retinal explants were cultured till PN28, during which they were treated with 10 ng/ml -GST or -GST. The spatiotemporal expression of both GST isoforms was closely similar: early presence in ganglion cell layer after which staining became restricted to Müller cells (particularly in the endfeet) and horizontal cell fibers in both rd1/rd1 and / . Doublets of -GST and -GST were detected by Western blot analysis. Densitometry of these bands indicated steady reduction of -GST content in rd1/rd1 retina starting from the second postnatal week. When -GST and -GST were added exogenously to rd1/rd1 explants, photoreceptor rescue was produced that was more prominent in PN2 than in PN7 explants and more effective by -GST than -GST. We propose that -GST neuroprotection is mediated by reduction of tissue oxidative stress. © 2005 Published by Elsevier Ltd on behalf of IBRO.