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A.S. Pawar, N.M. Qtaishat, D.R. Pepperberg; Photoreceptor Recovery in abcr–/– and Wildtype Mice Following Weak Bleaching of Rhodopsin . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4736.
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The ABCR protein of rod outer segments facilitates the movement of all–trans retinal from the disk lumen to the rod cytosol and thus plays an important role in the retinoid visual cycle. Weng et al. (1) examined recovery of the ERG a–wave in ABCR–deficient mice (abcr–/–) and found, by comparison with wildtype controls, sluggish a–wave recovery in the abcr–/– following about 45% rhodopsin bleaching. We investigated how ABCR deficiency influences rod dark adaptation in young mice subjected to a relatively weak bleach.
abcr–/– and wildtype mice (6–12 weeks) were dark–adapted overnight and anesthetized with ketamine/xylazine. Rod photoresponses were analyzed by paired–flash ERGs (2,3). The bleach (20 flashes delivered over 100 s, cumulatively 9.5x103 sc cd s m–2) was estimated at ∼1% based on wildtype data. Recovery of the derived rod response to the bleaching light was determined from responses to bright probe flashes presented at intervals of about 4 min after the bleach. The derived response to a weak (0.3 sc cd s m–2) test flash was determined in paired–flash trials (test–probe interval: 80 ms (2)).
In both abcr–/– and wildtype, recovery of the derived response to the bleaching light displayed a transient overshoot, i.e., fell temporarily to a level below the pre–bleach baseline. Simple exponential functions were fitted to data obtained at post–bleach times up to the overshoot trough. For abcr–/– mice, the determined exponential time constant, 2.68 ± 0.63 min (n = 4), was significantly less than the 9.45 ± 3.58 min (n = 4) value obtained for wildtype mice (P = 0.009). Normalized amplitudes of the dark–adapted derived response to the weak test flash were 0.69 ± 0.04 (n=6) for abcr–/– and 0.72 ± 0.07 (n=4) for wildtype; these values did not significantly differ, arguing against differences in bleaching efficacy as the basis of the difference in the above time constants. Recovery kinetics of the derived response to the weak test flash did not significantly differ in abcr–/– vs. wildtype.
Results obtained for the derived response to the bleaching light indicate, for relatively young mice and ∼1% rhodopsin bleaching, faster recovery of the rod membrane current in the abcr–/– as compared to wildtype. This relationship of recovery kinetics, which differs from that observed with about 45% bleaching (1), suggests that ABCR deficiency can directly or indirectly prime the recovery of rod circulating current after low bleaches. (1) Weng et al. (1999) Cell 98:13–23. (2) Hetling & Pepperberg (1999) J. Physiol. 516:593–609.(3) Kang Derwent et al. (2002) J. Physiol. 541:201–218.
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