PUBLICATION
Retinoic acid signaling is essential for maintenance of the blood-retinal barrier
- Authors
- Pollock, L.M., Xie, J., Bell, B.A., Anand-Apte, B.
- ID
- ZDB-PUB-180607-11
- Date
- 2018
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32(10): 5674-5684 (Journal)
- Registered Authors
- Anand-Apte, Bela, Pollock, Lana, Xie, Jing
- Keywords
- tight junctions, vasculature, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified/genetics
- Animals, Genetically Modified/metabolism
- Blood-Retinal Barrier/metabolism*
- Blood-Retinal Barrier/pathology
- Retinal Dehydrogenase/genetics
- Retinal Dehydrogenase/metabolism
- Retinoic Acid 4-Hydroxylase/genetics
- Retinoic Acid 4-Hydroxylase/metabolism
- Signal Transduction/drug effects*
- Signal Transduction/genetics
- Tretinoin*/pharmacokinetics
- Tretinoin*/pharmacology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 29874129 Full text @ FASEB J.
Citation
Pollock, L.M., Xie, J., Bell, B.A., Anand-Apte, B. (2018) Retinoic acid signaling is essential for maintenance of the blood-retinal barrier. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 32(10):5674-5684.
Abstract
The predominant function of the blood-retinal barrier (BRB) is to maintain retinal homeostasis by regulating the influx and efflux between the blood and retina. Breakdown of the BRB occurs in a number of ocular diseases that result in vision loss. Understanding the molecular and cellular pathways involved in the development and maintenance of the BRB is critical to developing therapeutics for these conditions. To visualize the BRB in vivo, we used the transgenic Tg(l-fabp:DBP-EGFP:flk1:mCherry) zebrafish model that expresses vitamin D binding protein (a member of the albumin gene family) tagged to green fluorescent protein. Retinoic acid (RA) plays a number of important roles in vertebrate development and has been shown to play a protective role during inflammation-induced blood-brain barrier disruption. The role of RA in BRB development and maintenance remains unknown. To disrupt RA signaling, Tg(l-fabp:DBP-EGFP:flk1:mCherry) zebrafish were treated with N, N-diethylaminobenzaldehyde and 4-[(1E)-2-[5,6-dihydro-5,5-dimethyl-8-(2-phenylethynyl)-2-naphthalenyl]ethenyl]benzoic acid, which are antagonists of retinal dehydrogenase and the RA receptor, respectively. Treatment with either compound resulted in BRB disruption and reduced visual acuity, whereas cotreatment with all-trans RA effectively rescued BRB integrity. Additionally, transgenic overexpression of Cyp26a1, which catalyzes RA degradation, resulted in breakdown of the BRB. Our results demonstrate that RA signaling is critical for maintenance of the BRB and could play a role in diseases such as diabetic macular edema.-Pollock, L. M., Xie, J., Bell, B. A., Anand-Apte, B. Retinoic acid signaling is essential for maintenance of the blood-retinal barrier.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping