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Wengtse Lam, Jody A. Summers Rada, Lindsey R. Hollaway, Nan Li, Joseph L. Napoli; Regulation of Choroidal Retinoic Acid Synthesis in Chick Eyes During Recovery from Induced Myopia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6289.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that RALDH2 is the major aldehyde dehydrogenase expressed in the chick choroid and may be responsible for increased retinoic acid (RA) synthesis by the choroid in response to myopic defocus. Endogenous RA concentration is determined by the balance between RA synthesis by RALDH2 and its catabolism by the CYP26 family of enzymes. Therefore, the present study compares transcript levels of RALDH2 and CYP26 with endogenous levels of RA in order to provide insights into choroidal retinoic acid metabolism during visually regulated eye growth.
Myopia was induced in chicks by form deprivation (FD) for 10 days, followed by up to 15 days of recovery. RALDH2 and CYP26 mRNA were measured from total RNA isolated from control and treated choroids following 0 - 15 days of recovery by real-time PCR. Newly synthesized and endogenous RA were measured from isolated choroids following 3 hrs of organ culture (in medium + choroid) with and without the aldehyde dehydrogenase inhibitor, disulfiram, using LC-tandem MS quantification.
RALDH2 mRNA pools were not significantly different in choroids following 10 days of FD (0 hrs recovery), but were elevated in choroids following 12 hrs of recovery (↑60% , p< 0.01), peaked at 24 hrs (↑188%, p < 0.01) and returned to control levels by 8 days of recovery. In contrast, CYP26 transcript pools were significantly elevated in treated eyes at 0 hrs of recovery, dropped to control levels by 12 hrs of recovery, and increased dramatically in both control and treated eyes by 15 days (↑17 and 14 fold, respectively). RA concentration was significantly higher in organ cultures of treated choroids following 24 hrs and remained elevated through 15 days of recovery (↑ 96 % - 72↑%, respectively, p<0.01). No significant differences were detected in RA concentration between control and treated choroids following incubation with disulfiram.
These results suggest that RALDH2 expression may be responsible for initial increased RA synthesis during recovery, but additional regulatory mechanisms, including changes in CYP26 activity may be involved in regulating endogenous levels and/or bioavailablity of choroidal RA.
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