Abstract
Purpose:
Retinitis pigmentosa (RP) includes a large group of inherited retinal disorders that cause progressive loss of retinal function. The rd10 mouse strain is a newly described model of retinal degeneration that bears a point mutation in exon 13 of the beta subunit of the cGMP phosphodiesterase gene. In previous studies we have shown that the decrease of GSH is related to photoreceptor cell death. Moreover, it is known that variations in glutathione (GSH), glutathione disulfide (GSSG), reflect oxidative stress and that oxidation in GSH may lead to disease susceptibility. Alterations in amino acid metabolism have also been observed in several different models of inherited retinal degeneration, particularly it has been reported an increase in free glutamate in rd1 mice retinas. The purpose of this study was to investigate glutathione metabolism and oxidative DNA damage in the retina of rd10 mice.
Methods:
Animals were treated in accordance to the ARVO statement for the use of animals in ophthalmic and vision research. We obtained retinas from wild type and rd10 mice at different postnatal days (PN15, 17, 21 and 28), and levels of GSH, GSSG, and Glutamate were determined by HPLC. TUNEL and 8-hydroxy deoxyguanosine stainings were also performed in retinal sections of mice at different PN days.
Results:
Retinal glutamate concentration was increased in the rd10 mice at all PN days. GSH was decreased in rd10 retinas compared to control retinas only when the degenerative process becomes detectable. No changes in GSSG concentrations were observed. The number of TUNEL and 8-hydroxy deoxyguanosine positive cells was increased with age in rd10 retinas mice until PN21.
Conclusions:
We confirm the importance of glutathione and glutamate metabolism is in this animal model of RP, though further studies are needed.
Keywords: 634 oxidation/oxidative or free radical damage •
695 retinal degenerations: cell biology •
688 retina