QLT091001, a 9-cis-Retinal Analog, Is Well-Tolerated by Retinas of Mice with Impaired Visual Cycles
Open accessAbstract
PURPOSE: Investigate whether retinas of mice with impaired retinal cycles exposed to light or kept in the dark tolerate prolonged high-dose administration of QLT091001, which contains as an active ingredient, the 9-cis-retinal precursor, 9-cis-retinyl acetate. METHODS: Four- to six-week-old Lrat(-/-) and Rpe65(-/-) mice (n = 126) as well as crossbred Gnat1(-/-) mice lacking rod phototransduction (n = 110) were gavaged weekly for 6 months with 50 mg/kg QLT091001, either after being kept in the dark or after light bleaching for 30 min/wk followed by maintenance in a 12-hour light ≤ 10 lux)/12-hour dark cycle. Retinal health was monitored by spectral-domain optical coherent tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO) every other month and histological, biochemical, and visual functional analyses were performed at the end of the experiment. Two-photon microscopy (TPM) was used to observe retinoid-containing retinosome structures in the RPE. RESULTS: Retinal thickness and morphology examined by SD-OCT were well maintained in all strains treated with QLT091001. No significant increases of fundus autofluorescence were detected by SLO imaging of any strain. Accumulation of all-trans-retinyl esters varied with genetic background, types of administered compounds and lighting conditions but retinal health was not compromised. TPM imaging clearly revealed maintenance of retinosomes in the RPE of all mouse strains tested. CONCLUSIONS: Retinas of Lrat(-/-), Rpe65(-/-), and crossbred Gnat1(-/-) mice tolerated prolonged high-dose QLT091001 treatment well.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In contrast to other cell types, an overdose of all-trans-retinol does not result in excessive accumulation of retinyl esters in the RPE.
“In contrast to other cell types, an overdose of all-trans-retinol does not result in excessive accumulation of retinyl esters in the RPE.567,575”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [575]
The Results (Fig. 6B; page unavailable) report only a mild increase in retinyl esters in wild-type mouse eyes after all-trans-retinyl acetate treatment. But the Discussion reports more than a threefold increase in treated Rpe65-deficient mice. The paper does not compare the RPE with other cell types, so it does not support the claim as a general statement about the RPE. (LLM, conf=0.84)
Experimental — accuracy not yet measuredReplacement therapy with synthetic 9-cis-retinyl acetate (QLT091001) slowed retinal degeneration and improved retinal function in animal models.
“Replacement therapy of missing 11-cis-retinol by synthetic 9-cis-retinyl acetate (QLT091001) has shown promising results in animal models, as it slowed the rate of retinal degeneration and improved the retinal function [118,119].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [119]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 60 · Cited by 41
Research works printed but not linked: 3
- Fan J, Rohrer B, Frederick JM, Baehr W, Crouch RK. Rpe65À/À and LratÀ/À mice: comparable models of leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2008;49:2384-2389.
- Znoiko SL, Rohrer B, Lu K, Lohr HR, Crouch RK, Ma JX. Downregulation of cone-specific gene expression and degen- eration of cone photoreceptors in the Rpe65À/À mouse at early ages. Invest Ophthalmol Vis Sci. 2005;46:1473-1479.
- Maeda T, Golczak M, Maeda A. Retinal photodamage mediated by all-trans-retinal. Photochem Photobiol. 2012;88:1309- 1319.
- Authors
- Maeda, T., Dong, Z., Jin, H., Sawada, O., Gao, S., Utkhede, D., Monk, W., Palczewska, G., & Palczewski, K.
- Affiliations
- Case Western Reserve University (US)
- Polgenix (United States) (US)
- From the Departments of Ophthalmology and
- QLT (Canada) (CA)
- Polgenix, Inc., Cleveland, Ohio; and
- Corresponding author
- Maeda, Tadao
- Dong, Zhiqian
- Jin, Hui
- Sawada, Osamu
- Gao, Songqi
- Utkhede, Deepank
- Monk, Wendy
- Palczewski, Krzysztof
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2013-01-17
- Volume
- 54
- Issue
- 1
- Pages
- 455
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC4686220
- OpenAlex
- W2051474291
- Cited by
- 41
- References
- 60
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 4
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Case Western Reserve University
- National Institutes of Health
- National Eye Institute (R24EY021126)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- rod phototransduction, retinal pigment epithelium, retinal thickness, fundus autofluorescence
- MeSH terms
- Animals, Dark Adaptation, Disease Models, Animal, Diterpenes, Electroretinography, Female, Isomerism, Male, Mice, Inbred C57BL, Pigment Epithelium of Eye, Retinaldehyde, Vision Disorders, Retinal Cone Photoreceptor Cells, Tomography, Optical Coherence, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
