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Y. E. Wen, D. M. Niculescu, V. E. Wotring, T. W. Kraft; Patho-Physiology of Rod Photoreceptors Under Stress -Retinal Degeneration Reshape the Light Responses of Surviving Rod Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1046.
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© ARVO (1962-2015); The Authors (2016-present)
Despite rapid progress in the investigation of normal rod physiology in recent years, we still have little information about how degenerative diseases disturb the normal rod physiology at the single cell level. We set out to test the hypothesis that degenerative stress can induce altered rod physiology in a light-induced retinal degeneration model and the Royal College of Surgeons rat (RCS rat).
Dark-adapted photoresponses were recorded from single rod photoreceptors in isolated retina. Light damaged rods from albino rats were recorded at 3 days, 5 days, 15 days, and 30 days after constant white light exposure of 280lux for 240 consecutive hours. The RCS rat rods were recorded at postnatal (PN) day 16, 23, 30, 45, and 52. The suction electrode recordings were conducted as described previously (Kraft et al., 2005, Mol Vis). Results were compared to data from appropriate age-matched controls. All single cell physiology parameters were measured from 13-25 rods. Preliminary mRNA analysis has been done.
Significant loss of photoreceptors was observed in the two RP models studied. The rods from light damaged rat and the RCS rat shared reduced sensitivity and accelerated recovery in the light response. This altered physiology was most obvious 3-5 days after light damage for the albino rat and after PN45 for the RCS rat. The altered rod physiology for RCS rat progressed with age. However, the altered physiology of light damaged rat rods recovered almost fully to control values after 30 days. Specifically, the I 1/2 (flash strength that elicits half-maximal response amplitude) was increased by more than four-fold at PN45 for RCS rat and about two-fold 3 days after light damage for albino rat. Dominant time constant (tau) of albino rat was decreased by almost half at 3 days and a third at 5 days after light damage but recovered to the control value by 15 days. The tau value of the RCS rat was decreased by almost a third at PN day 30 and half at PN day 45. When compared to standard housekeeping genes the mRNA of R9AP and RGS9 (GTPase accelerating proteins) decreased in the degenerate animals.
We found that an altered form of light response exists in two widely used models for RP: Light damage model and the RCS rat. The reduced sensitivity and accelerated recovery in rod light response share commonality with the physiology of pig rods containing rhodopsin mutations (P347L or P347S) (Kraft et al., 2005, Mol Vis).
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