Reduced Retinal Na+/K+-ATPase Activity in cAMP-Treated Chick Eyes with Imposed Hyperopic Defocus

Abstract

Purpose: : We have previously demonstrated that intravitreal cAMP injection abolishes the lens-induced myopic shift and triggers an upregulation of apolipoprotein A1 (ApoA1) protein expression in young chicks. It has been shown that cAMP modulates the activity of Na⁺/K⁺-ATPase, an important transmembrane enzyme responsible for active transport and signal transduction. Additionally, Na⁺/K⁺-ATPase has been demonstrated to regulate ApoA1 transcription rate. In this study, we aimed to examine the effect of cAMP on retinal Na⁺/K⁺-ATPase activity in chicks with imposed hyperopic defocus.

Methods: : White Leghorn chicks (Gallus gallus) were used and at 8-day after hatching, both eyes were mounted with a -10D lens glued on Velcro rings. At the same time, the experimental eye was injected intravitreally with 1mM 8-Bromo-cAMP (8-Br-cAMP) and the fellow control eye with saline once daily for 4 consecutive days. Biometric measurements and retinoscopy were conducted both before and after drug treatment. Thereafter, the chicks were sacrificed and the retina was isolated for ApoA1 expression and Na⁺/K⁺-ATPase activity measurements.

Results: : Intravitreal injection of 1mM 8-Br-cAMP abolished the lens-induced myopia. The change in refractive error in cAMP-treated eye (n=13, p<0.01) was accompanied by choroidal thickening (p<0.01), decrease in vitreous chamber depth (p<0.01) and axial length (p<0.05) compared with the fellow eye. Moreover, ApoA1 protein expression was upregulated by more than 2 fold in cAMP-treated retina as compared to saline-treated eye (n=9, p<0.01). Concomitantly, Na⁺/K⁺-ATPase activity was downregulated by about 20% in cAMP-treated retina (n=10, p<0.01).

Conclusions: : Our results showed a reduction of retinal Na⁺/K⁺-ATPase activity concomitant with an upregulation of ApoA1 protein expression in cAMP-treated chick eye subject to hyperopic defocus. This finding indicates that cAMP may alter the retinal transport activity and/or energy metabolism through the inhibition of retinal Na⁺/K⁺-ATPase. Further studies are needed to determine the precise relationship between the activity of Na⁺/K⁺-ATPase and the expression level of ApoA1.

Keywords: NaK ATPase • myopia