Tauroursodeoxycholic acid preservation of photoreceptor structure and function in the rd10 mouse through postnatal day 30.
OBJECTIVE
Retinitis pigmentosa (RP) is a progressive neurodegenerative disease resulting in blindness for which there is no current treatment. Although the members of the family of RP diseases differ in etiology, their outcomes are the same: apoptosis of rods and then by cones. Recently, the bile acid tauroursodeoxycholic acid (TUDCA) has been shown to have antiapoptotic properties in neurodegenerative diseases, including those of the retina. In this study the authors examined the efficacy of TUDCA on preserving rod and cone function and morphology at postnatal day 30 (P30) in the rd10 mouse, a model of RP.


METHODS
Wild-type C57BL/6J and rd10 mice were systemically injected with TUDCA (500 mg/kg) every 3 days from P6 to P30 and were compared with vehicle (0.15 M NaHCO(3)). At P30, retinal function was measured with electroretinography, and morphologic preservation of the rods and cones was assessed with immunohistochemistry.


RESULTS
Dark-adapted electroretinographic (ERG) responses were twofold greater in rd10 mice treated with TUDCA than with vehicle, likewise light-adapted responses were twofold larger in TUDCA-treated mice than in controls at the brightest ERG flash intensities. TUDCA-treated rd10 retinas had fivefold more photoreceptors than vehicle-treated retinas. TUDCA treatments did not alter retinal function or morphology of wild-type mice when administered to age-matched mice.


CONCLUSIONS
TUDCA is efficacious and safe in preserving vision in the rd10 mouse model of RP when treated between P6 and P30. At P30, a developmental stage at which nearly all rods are absent in the rd10 mouse model of RP, TUDCA treatment preserved rod and cone function and greatly preserved overall photoreceptor numbers.
Phillips
M Joe
MJ
Rehabilitation Research and Development Center, Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA 30033, USA.
Walker
Tiffany A
TA
Choi
Hee-Young
HY
Faulkner
Amanda E
AE
Kim
Moon K
MK
Sidney
Sheree S
SS
Boyd
Amber P
AP
Nickerson
John M
JM
Boatright
Jeffrey H
JH
Pardue
Machelle T
MT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D002467:Cell Nucleus; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000503:physiopathology*; D017299:Rod Opsins / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D017299:Rod Opsins; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine