ArticleInvestigative ophthalmology & visual science2015
In Vivo Visualization of Endoplasmic Reticulum Stress in the Retina Using the ERAI Reporter Mouse.
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 20 papers.
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Who cites it
20 citing papers in PubMed.
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Preclinical dose response study shows NR2E3 can attenuate retinal degeneration in the retinitis pigmentosa mouse model RhoGene therapy · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- The RBPMSiScience · 2023Article
- Deletion of the Unfolded Protein Response Transducer IRE1α Is Detrimental to Aging Photoreceptors and to ER Stress-Mediated Retinal Degeneration.Investigative ophthalmology & visual science · 2023Article
- Lysine Ubiquitylation Drives Rhodopsin Protein Turnover.Advances in experimental medicine and biology · 2023Article
- Network biology analysis of P23H rhodopsin interactome identifies protein and mRNA quality control mechanisms.Scientific reports · 2022Article
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- ATF6 is required for efficient rhodopsin clearance and retinal homeostasis in the P23H rho retinitis pigmentosa mouse model.Scientific reports · 2021Article
- Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa.Gene therapy · 2021Article
- Influence of Oxidative Stress on Time-Resolved Oxygen Detection by [Ru(Phen)Molecules (Basel, Switzerland) · 2021Article
- Retinal Damage in Amyotrophic Lateral Sclerosis: Underlying Mechanisms.Eye and brain · 2021Review
- Epigallocatechin Gallate Slows Retinal Degeneration, Reduces Oxidative Damage, and Modifies Circadian Rhythms in P23H Rats.Antioxidants (Basel, Switzerland) · 2020Article
- Establishment and validation of an endoplasmic reticulum stress reporter to monitor zebrafish ATF6 activity in development and disease.Disease models & mechanisms · 2020Article
- Tunicamycin-induced photoreceptor atrophy precedes degeneration of retinal capillaries with minimal effects on retinal ganglion and pigment epithelium cells.Experimental eye research · 2019Article
- ER stress and unfolded protein response in ocular health and disease.The FEBS journal · 2019Review
- Autosomal recessive cone-rod dystrophy can be caused by mutations in the ATF6 gene.European journal of human genetics : EJHG · 2017Article
- Genetic dissection of anterior segment dysgenesis caused by aDisease models & mechanisms · 2017Article
- Achromatopsia mutations target sequential steps of ATF6 activation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
9 authors.
Funding
Abstract
purposeEndoplasmic reticulum (ER) stress activates inositol requiring enzyme 1 (IRE1), a key regulator of the unfolded protein response. The ER stress activated indicator (ERAI) transgenic mouse expresses a yellow fluorescent GFP variant (Venus) when IRE1 is activated by ER stress. We tested whether ERAI mice would allow for real-time longitudinal studies of ER stress in living mouse eyes.
methodsWe chemically and genetically induced ER stress, and qualitatively and quantitatively studied the Venus signal by fluorescence ophthalmoscopy. We determined retinal cell types that contribute to the signal by immunohistology, and we performed molecular and biochemical assays using whole retinal lysates to assess activity of the IRE1 pathway.
resultsWe found qualitative increase in vivo in fluorescence signal at sites of intravitreal tunicamycin injection in ERAI eyes, and quantitative increase in ERAI mice mated to RhoP23H mice expressing ER stress-inducing misfolded rhodopsin protein. As expected, we found that increased Venus signal arose primarily from photoreceptors in RhoP23H/+;ERAI mice. We found increased Xbp1S and XBP1s transcriptional target mRNA levels in RhoP23H/+;ERAI retinas compared to Rho+/+;ERAI retinas, and that Venus signal increased in ERAI retinas as a function of age.
conclusionsFluorescence ophthalmoscopy of ERAI mice enables in vivo visualization of retinas undergoing ER stress. ER stress activated indicator mice enable identification of individual retinal cells undergoing ER stress by immunohistochemistry. ER stress activated indicator mice show higher Venus signal at older ages, likely arising from amplification of basal retinal ER stress levels by GFP's inherent stability.
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