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B. C. Oveson, S. F. Hackett, T. Iwase, S. Lee, T. W. Sedlak, S. H. Snyder, P. A. Campochiaro, J. U. Sung; Constituents of Bile, Bilirubin and TUDCA, Protect Against Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3732.
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To assess the effects of bilirubin, a physiologic cytoprotectant, and tauroursodeoxycholic acid (TUDCA) in the rd10+/+ mice and mice with light-induced retinal degeneration.
Subcutaneous injections of bilirubin or TUDCA were administered to rd10+/+ mice every three days from postnatal day (P) 6 to P49. Retinal function was assessed by scotopic and photopic electroretinograms (ERGs) at P30 and P50. Photoreceptor cell survival was assessed by measuring cell density of peanut-agglutinin-stained retinal whole mounts and outer nuclear layer (ONL) thickness. Albino BALB/c mice were injected 24 hours and 1 hour before exposure to 8 hours of light at an intensity of 5,000 lux. Photoreceptor survival was assessed by scotopic and photopic ERGs taken 24 hours and 7 days after light exposure.
At P30, bilirubin- (n=10) and TUDCA-treated rd10+/+ mice (n=6) showed higher (P<0.02) peak mean scotopic ERG (µV) a-wave amplitudes (76+4 and 76+2, respectively) compared to vehicle-treated littermates (52+4 and 45+5). Mean scotopic b-wave amplitudes for bilirubin (377+33) and TUDCA (367+30) groups were also higher (P<0.05) compared to vehicle-treated littermates (193+45 and 267+28, respectively). Mean photopic b-wave amplitudes for bilirubin- (242+19) and TUDCA-treated mice (254+22) were greater (P<0.01) than those in vehicle-treated littermates (148+23 and 131+19). ONL thickness measurements were greater (P<0.05) at three out of the six measurement locations in the bilirubin group, and at four out of six locations in the TUDCA group. At P50, bilirubin- (n=9) and TUDCA-treated rd10+/+ mice (n=8) showed higher (P<0.05) peak mean photopic b-wave amplitudes (55+8 and 83+15) compared to untreated littermates (26+3). Mean cone cell density (cones/0.0529 mm2) was greater for bilirubin-treated rd10+/+ (215+30), and TUDCA-treated rd10+/+ (278+21) compared to untreated rd10+/+ (93+13). Light-exposed BALB/c mice treated with bilirubin or TUDCA showed significant preservation of ERG function compared to untreated mice.
Treatment with bilirubin or TUDCA effectively slowed photoreceptor degeneration in rd10+/+ mice through P50 and reduced light-induced photoreceptor death in BALB/c mice.
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