TY - JOUR
T1 - Retinoic acid maintains function of neural crest–derived ocular and craniofacial structures in adult zebrafish
AU - Chawla, Bahaar
AU - Swain, William
AU - Williams, Antionette L.
AU - Bohnsack, Brenda L.
N1 - Funding Information:
The authors thank Mitchell Gillett and the Kellogg Eye Center Morphology and Imaging Module for technical assistance. Supported by a Grant from the National Eye Institute of the National Institutes of Health (K08EY022912-01) and the Alcon Research Institute. Disclosure: B. Chawla, None; W. Swain, None; A.L. Williams, None; B.L. Bohnsack, None
Funding Information:
The authors thank Mitchell Gillett and the Kellogg Eye Center Morphology and Imaging Module for technical assistance. Supported by a Grant from the National Eye Institute of the National Institutes of Health (K08EY022912-01) and the Alcon Research Institute.
Publisher Copyright:
© 2018 The Authors.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/4
Y1 - 2018/4
N2 - PURPOSE. Retinoic acid (RA) is required for embryonic formation of the anterior segment of the eye and craniofacial structures. The present study further investigated the role of RA in maintaining the function of these neural crest–derived structures in adult zebrafish. METHODS. Morphology and histology were analyzed by using live imaging, methylacrylate sections, and TUNEL assay. Functional analysis of vision and aqueous humor outflow were assayed with real-time imaging. RESULTS. Both decreased and increased RA signaling altered craniofacial and ocular structures in adult zebrafish. Exogenous treatment with all-trans RA for 5 days resulted in a prognathic jaw, while inhibition of endogenous RA synthesis through treatment with 4-diethylamino-benzaldehyde (DEAB) decreased head height. In adult eyes, RA activity was localized to the retinal pigment epithelium, photoreceptors, outer plexiform layer, inner plexiform layer, iris stroma, and ventral canalicular network. Exogenous RA increased apoptosis in the iris stroma and canalicular network in the ventral iridocorneal angle, resulting in the loss of these structures and decreased aqueous outflow. DEAB, which decreased RA activity throughout the eye, induced widespread apoptosis, resulting in corneal edema, cataracts, retinal atrophy, and loss of iridocorneal angle structures. DEAB-treated fish were blind with no optokinetic response and no aqueous outflow from the anterior chamber. CONCLUSIONS. Tight control of RA levels is required for normal structure and function of the adult anterior segment. These studies demonstrated that RA plays an important role in maintaining ocular and craniofacial structures in adult zebrafish.
AB - PURPOSE. Retinoic acid (RA) is required for embryonic formation of the anterior segment of the eye and craniofacial structures. The present study further investigated the role of RA in maintaining the function of these neural crest–derived structures in adult zebrafish. METHODS. Morphology and histology were analyzed by using live imaging, methylacrylate sections, and TUNEL assay. Functional analysis of vision and aqueous humor outflow were assayed with real-time imaging. RESULTS. Both decreased and increased RA signaling altered craniofacial and ocular structures in adult zebrafish. Exogenous treatment with all-trans RA for 5 days resulted in a prognathic jaw, while inhibition of endogenous RA synthesis through treatment with 4-diethylamino-benzaldehyde (DEAB) decreased head height. In adult eyes, RA activity was localized to the retinal pigment epithelium, photoreceptors, outer plexiform layer, inner plexiform layer, iris stroma, and ventral canalicular network. Exogenous RA increased apoptosis in the iris stroma and canalicular network in the ventral iridocorneal angle, resulting in the loss of these structures and decreased aqueous outflow. DEAB, which decreased RA activity throughout the eye, induced widespread apoptosis, resulting in corneal edema, cataracts, retinal atrophy, and loss of iridocorneal angle structures. DEAB-treated fish were blind with no optokinetic response and no aqueous outflow from the anterior chamber. CONCLUSIONS. Tight control of RA levels is required for normal structure and function of the adult anterior segment. These studies demonstrated that RA plays an important role in maintaining ocular and craniofacial structures in adult zebrafish.
KW - Aqueous humor outflow
KW - Neural crest
KW - Retinoic acid
KW - Vitamin A
KW - Zebrafish
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U2 - 10.1167/iovs.17-22845
DO - 10.1167/iovs.17-22845
M3 - Article
C2 - 29677354
AN - SCOPUS:85045116599
VL - 59
SP - 1924
EP - 1935
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 5
ER -