TUDCA slows retinal degeneration in two different mouse models of retinitis pigmentosa and prevents obesity in Bardet-Biedl syndrome type 1 mice

Arlene V Drack; Alina V Dumitrescu; Sajag Bhattarai; Daniel Gratie; Edwin M Stone; Robert Mullins; Val C Sheffield

doi:10.1167/iovs.11-8544

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TUDCA slows retinal degeneration in two different mouse models of retinitis pigmentosa and prevents obesity in Bardet-Biedl syndrome type 1 mice

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TUDCA slows retinal degeneration in two different mouse models of retinitis pigmentosa and prevents obesity in Bardet-Biedl syndrome type 1 mice

Arlene V Drack, Alina V Dumitrescu, Sajag Bhattarai, Daniel Gratie, Edwin M Stone, Robert Mullins and Val C Sheffield

Investigative ophthalmology & visual science, Vol.53(1), pp.100-106

01/05/2012

DOI: 10.1167/iovs.11-8544

PMCID: PMC3292352

PMID: 22110077

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Abstract

To evaluate and compare the protective effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration in different models of retinal degeneration (RD) in mice. Bbs(M390R/M390R) mice were injected subcutaneously twice a week, from P40 to P120, and rd10 mice were injected every 3 days from P6 to P38 with TUDCA or vehicle (0.15 M NaHCO(3)). Rd1 and rd16 mice were injected daily from P6 to P30 with TUDCA or vehicle. Retinal structure and function were determined at multiple time points by electroretinography (ERG), optical coherence tomography (OCT), and histology. The amplitude of ERG b-waves was significantly higher in TUDCA-treated Bbs1 and rd10 animals than in controls. Retinal thickness on OCT was slightly greater in treated Bbs1 animals than in the controls. Histologically, outer segments were preserved, and the outer nuclear layer was significantly thicker in the treated Bbs1 and rd10 mice than in the controls. Bbs1(M390R/M390R) mice developed less obesity than the control Bbs1(M390R/M390R) while receiving TUDCA. The Rd1 and rd16 mice showed no improvement with TUDCA treatment, and the rd1 mice did not have normal weight gain during treatment. TUDCA treatment preserved ERG b-waves and the outer nuclear layer in Bbs1(M390R/M390R) mice, and prevented obesity assessed at P120. TUDCA treatment preserved ERG b-waves and the outer nuclear layer in the rd10 mice to P30. TUDCA is a prime candidate for treatment of humans with retinal degeneration, especially those with Bardet-Biedl syndrome, whom it may help not only with the vision loss, but with the debilitating obesity as well.

Cholagogues and Choleretics - administration & dosage

Microtubule-Associated Proteins - genetics

Retinal Degeneration - drug therapy

Tomography, Optical Coherence

Retina - physiopathology

Retinitis Pigmentosa - drug therapy

Bardet-Biedl Syndrome - drug therapy

Retinal Degeneration - physiopathology

Cholagogues and Choleretics - therapeutic use

Electroretinography - drug effects

Animals

Injections, Subcutaneous

Obesity - prevention & control

Bardet-Biedl Syndrome - genetics

Mice

Retinitis Pigmentosa - physiopathology

Taurochenodeoxycholic Acid - administration & dosage

Taurochenodeoxycholic Acid - therapeutic use

Disease Models, Animal

Details

Title: Subtitle: TUDCA slows retinal degeneration in two different mouse models of retinitis pigmentosa and prevents obesity in Bardet-Biedl syndrome type 1 mice
Creators: Arlene V Drack - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa 52242, USA
Alina V Dumitrescu
Sajag Bhattarai
Daniel Gratie - University of Iowa
Edwin M Stone
Robert Mullins
Val C Sheffield
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.53(1), pp.100-106
DOI: 10.1167/iovs.11-8544
PMID: 22110077
PMCID: PMC3292352
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY-17168 / NEI NIH HHS Howard Hughes Medical Institute R01 EY-110298 / NEI NIH HHS R01 EY017168 / NEI NIH HHS
Language: English
Date published: 01/05/2012
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979954902771

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