Tauroursodeoxycholic Acid Prevents Retinal Degeneration in Transgenic P23H Rats

Fernández‐Sánchez, Laura; Lax, Pedro; Pinilla, Isabel; Martı́n-Nieto, José; Cuenca, Nicolás

doi:10.1167/iovs.11-7496

Cited by 87 publications

(89 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is a close dependence of cone integrity on rod integrity, compared to the life-long persistence of cone function in the scotopic rat. 32 Reducing environmental lighting 35 in combination with other treatments 36 may delay retinal degeneration arising from rhodopsin mutations. Using green filters to repeatedly test the effect of therapeutic interventions in rats in vivo could minimize the light-induced damage.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Visual and Chromatic Functions in a Rodent Model of Retinal Degeneration

Segura

Sánchez‐Cano

Jarabo

et al. 2015

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

PURPOSE. We evaluated the photoreceptor response of pigmented P23H and normal pigmented Long Evans (LE) rats over time using functional tests in variable lighting conditions. METHODS.Pigmented P23H rats were studied by optomotor testing and electroretinogram (ERG) recordings at P30, P150, and P240. Pigmented LE rats were used as a normal wild-type control. Stimuli were modified with colored filters. Neutral density filters were used to reduce luminance.RESULTS. Age-related decreases in visual acuity (VA) and contrast sensitivity (CS) were observed in P23H rats. Good correlations in measurements without filter and with green filter were observed between LE and P23H P30 rat values. Differences between groups were smaller with red and purple filters. A strong relationship with luminance was observed in LE rats (VA and CS) and with P23H P30 rats (CS). A decline in the ERG responses of P23H rats was consistent with the gradual loss of photoreceptors. Differences in a-and b-wave amplitudes with different colored filters were negligible with the exception of the red filter, which resulted in smaller responses.CONCLUSIONS. Visual function parameters decreased with age in pigmented P23H rats. Irrespective of luminance, color filter, and retinal degeneration, minimum thresholds of VA and CS were found. Smaller differences than expected were found using color filters. Responses to functional tests at long wavelengths were observed, where there is very low photoreceptor spectral sensitivity. The use of filters with functional testing could minimize light-induced retinal damage in rats.Keywords: P23H, retinitis pigmentosa, optokinetic tracking, electroretinogram R ats are nocturnal animals with a rod-dominated retina. However, their retina also contains a small number of cones.1 Rats maintain an order of magnitude difference in the numbers of cones with maximum sensitivity in the short wavelength (S-cones, with a peak of 358 nm) compared to the middle and long wavelengths (ML-cones, peaking at approximately 509 nm).2,3 Middle and long wavelength cones constitute approximately 90% of cones; the other 10% are Scones that are thought to be UV-sensitive elements, but they probably do not appreciably contribute to the photopic system of the rat. 4 The maximum responses of the two types of cones and rods of rats have been widely studied by electroretinography (ERG), however the contribution of each type of cone to the visual system is not clear. 3,5 Retinitis pigmentosa (RP) is the most common form of inherited photoreceptor degeneration. 6,7 It comprises a group of diseases characterized by a progressive anatomical and functional loss of rod and cone photoreceptors.8 Autosomal dominant RP is responsible for most RP cases, 9 and most cases are due to rhodopsin mutations. Cones are lost after the rod degeneration. The transgenic albino P23H rat is a well-studied model of autosomal dominant RP. In pigmented RP rodent models, a progressive deterioration also occurs in retinal function and anatomy. Because an important role of retinal...

show abstract

Section: Discussionmentioning

confidence: 99%

Assessment of Visual and Chromatic Functions in a Rodent Model of Retinal Degeneration

Segura

Sánchez‐Cano

Jarabo

et al. 2015

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Frederick et al (60) then generated a P23H TG mouse on a rhodopsin knock-out background, and they reported that GHL (P23H)/ Rho Ϫ/Ϫ mice failed to form ROS and that P23H rhodopsin mainly accumulated in the outer nuclear layer. P23H TG rat line-3 is the most commonly used animal model for gene therapy and drug testing (12,21,22,(77)(78)(79)(80)(81)(82)(83), but immunochemistry showed rhodopsin is localized in the ROS of this TG rat (84). The P23H transgene has also been expressed in Xenopus, revealing an inner segment accumulation (10).…”

Section: Discussionmentioning

confidence: 99%

Inherent Instability of the Retinitis Pigmentosa P23H Mutant Opsin

Chen

Jastrzębska

Cao

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The P23H opsin mutant causes the blinding human disease, retinitis pigmentosa. Results: Molecular properties of bovine P23H mutant opsin were characterized in both in vitro and a transgenic C. elegans model. Conclusion: Thermally unstable P23H isorhodopsin containing correct disulfide bond can be slowly regenerated in transgenic C. elegans. Significance: This study produced novel information about the disease-causing P23H mutant opsin.

show abstract

“…Glycoursodeoxycholic acid counteracts bilirubin-induced neuronal death and synaptic changes [68]. UDCA and its conjugates could also alleviate other pathological conditions, such as stroke [69,70], spinal cord injury [71], neurodegenerative diseases [72][73][74], retinopathy [75,76], myocardial infarction [77], ischemia reperfusion syndromes [78], colon carcinogenesis [79,80], and psoriasis [81]. In a model of gonadal toxicity, Kwon et al reported that UDCA was effective in the prevention and treatment of 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD)-induced testicular damage in mice [82].…”

Section: Discussionmentioning

confidence: 99%

Testicular immunohistochemical and Ultrastructural changes associated with chronic cholestasis in rats: Effect of ursodeoxycholic acid

Mahmoud

2015

Life Sciences

View full text Add to dashboard Cite

Tauroursodeoxycholic Acid Prevents Retinal Degeneration in Transgenic P23H Rats

Abstract: TUDCA treatment was capable of preserving cone and rod structure and function, together with their contacts with their postsynaptic neurons. The neuroprotective effects of TUDCA make this compound potentially useful for delaying retinal degeneration in RP.

Cited by 87 publications

References 58 publications

Assessment of Visual and Chromatic Functions in a Rodent Model of Retinal Degeneration

Assessment of Visual and Chromatic Functions in a Rodent Model of Retinal Degeneration

Inherent Instability of the Retinitis Pigmentosa P23H Mutant Opsin

Testicular immunohistochemical and Ultrastructural changes associated with chronic cholestasis in rats: Effect of ursodeoxycholic acid

Contact Info

Product

Resources

About