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Bahaar Chawla, William Swain, Brenda L Bohnsack; Retinoic acid maintains the structure and function of aqueous outflow pathways in the adult zebrafish eye.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1732.
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© ARVO (1962-2015); The Authors (2016-present)
Retinoic acid (RA) regulation of cranial neural crest migration, survival and differentiation is critical for development of the anterior segment of the eye. However, the role of RA in the maintenance of the structure and function of the cornea, iris, and iridocorneal angle in the post-embryonic eye is unknown. In these studies, we use zebrafish to elucidate the role of RA in the adult anterior segment.
Adult zebrafish (1-2 yr old) were exposed to the pan-aldehyde dehydrogenase inhibitor, 4-diethylaminobenzaldehyde (DEAB, 10uM) to inhibit RA synthesis, all-trans RA (100nM), or dimethylsulfoxide (DMSO) control for 5 days. Optokinetic reflex (OKR) was used as assessment of functional vision pre- and post-treatment. Aqueous outflow through the ventral canalicular network was assessed in vivo. Fish were sacrificed and ocular structures were analyzed using TUNEL assay,phosphohistone-3 immunostaining, methylacrylate sections, and in situ hybridization.
Tight control of RA levels was required for visual function and maintenance of adult ocular structures. Treatment with DEAB, which inhibits endogenous RA synthesis, or exogenous RA disrupted smooth pursuit and saccadic eye movements on OKR testing. Decreased RA levels induced apoptosis throughout all layers of the retina and anterior segment of the eye resulting in loss of cellular architecture (H, arrow), corneal edema (I) and overall decreased eye size (G) compared to controls (A, B, C). This resulted in decreased aqueous outflow through the ventral canalicular network. Exogenous RA did not induce apoptosis in the anterior segment (D), but caused remodeling of the cornea (F, arrow) and ventral angle structures (E, arrow)) such that there was complete inhibition of aqueous outflow from the anterior chamber.
Tight control of RA levels was required for the maintenance of adult zebrafish ocular structures and visual function. Both increased and decreased RA levels disrupted aqueous outflow from the anterior chamber indicating that proper regulation of RA synthesis and degradation in the eye is key for visual function. Thus, RA may play a role in the adult eye in the pathogenesis of open angle glaucoma.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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