ArticleInvestigative ophthalmology & visual science2015
Targeting Caspase-12 to Preserve Vision in Mice With Inherited Retinal Degeneration.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
- Exploring caspase functions in mouse models.Apoptosis : an international journal on programmed cell death · 2024Review
- Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.Pharmaceutics · 2023Review
- Gene Therapy for Rhodopsin Mutations.Cold Spring Harbor perspectives in medicine · 2022Article
- Gene Therapy for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa.International ophthalmology clinics · 2021Article
- Endoplasmic reticulum stress: New insights into the pathogenesis and treatment of retinal degenerative diseases.Progress in retinal and eye research · 2020Review
- Ultrahigh Resolution Mouse Optical Coherence Tomography to Aid Intraocular Injection in Retinal Gene Therapy Research.Journal of visualized experiments : JoVE · 2018Article
- Translational attenuation and retinal degeneration in mice with an active integrated stress response.Cell death & disease · 2018Article
- GARP2 accelerates retinal degeneration in rod cGMP-gated cation channel β-subunit knockout mice.Scientific reports · 2017Article
- TNFa knockdown in the retina promotes cone survival in a mouse model of autosomal dominant retinitis pigmentosa.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe unfolded protein response is known to contribute to the inherited retinal pathology observed in T17M rhodopsin (T17M) mice. Recently it has been demonstrated that the endoplasmic reticulum stress-associated caspase-12 is activated during progression of retinal degeneration in different animal models. Therefore, we wanted to explore the role of caspase-12 in the mechanism of retinopathy in T17M mice and determine if inhibiting apoptosis in this way is a viable approach for halting retinal degeneration.
methodsOne, two-, and three-month-old C57BL6/J, caspase-12-/-, T17M, and T17M caspase-12-/- mice were analyzed by scotopic ERG, spectral-domain optical coherence tomography (SD-OCT), histology, quantitative (q)RT-PCR, and Western blot of retinal RNA and protein extracts. Calpain and caspase-3/7 activity assays were measured in postnatal (P) day 30 retinal extracts.
resultsCaspase-12 ablation significantly prevented a decline in the a- and b-wave ERG amplitudes in T17M mice during three months, increasing the amplitudes from 232% to 212% and from 160% to 138%, respectively, as compared to T17M retinas. The SD-OCT results and photoreceptor row counts demonstrated preservation of retinal structural integrity and postponed photoreceptor cell death. The delay in photoreceptor cell death was due to significant decreases in the activity of caspase-3/7 and calpain, which correlated with an increase in calpastatin expression.
conclusionsWe validated caspase-12 as a therapeutic target, ablation of which significantly protects T17M photoreceptors from deterioration. Although the inhibition of apoptotic activity alone was not sufficient to rescue T17M photoreceptors, in combination with other nonapoptotic targets, caspase-12 could be used to treat inherited retinopathy.
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