April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Constituents of Bile, Bilirubin and TUDCA, Protect Against Retinal Degeneration
Author Affiliations & Notes
  • B. C. Oveson
    Ophthalmology,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • S. F. Hackett
    Ophthalmology,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • T. Iwase
    Ophthalmology,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • S. Lee
    Ophthalmology,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • T. W. Sedlak
    Neuroscience,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • S. H. Snyder
    Neuroscience,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • P. A. Campochiaro
    Ophthalmology,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • J. U. Sung
    Ophthalmology,
    Johns Hopkins University Wilmer Eye Inst, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  B.C. Oveson, None; S.F. Hackett, None; T. Iwase, None; S. Lee, None; T.W. Sedlak, None; S.H. Snyder, None; P.A. Campochiaro, None; J.U. Sung, None.
  • Footnotes
    Support  NIH Grant EY015025-03, FFB Grant C-NP-0707-0419-JHU05, Knights Templar Eye Foundation
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3732. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To assess the effects of bilirubin, a physiologic cytoprotectant, and tauroursodeoxycholic acid (TUDCA) in the rd10+/+ mice and mice with light-induced retinal degeneration.

Methods: : 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.

Results: : 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.

Conclusions: : Treatment with bilirubin or TUDCA effectively slowed photoreceptor degeneration in rd10+/+ mice through P50 and reduced light-induced photoreceptor death in BALB/c mice.

Keywords: retinal degenerations: hereditary • retina • photoreceptors 
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