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Cyclic Adenosine Monophosphate Activates Retinal Apolipoprotein A1 Expression and Inhibits Myopic Eye Growth

Rachel Ka Man Chun¹, Sze Wan Shan¹, Thomas Chuen Lam¹

¹Laboratory of Experimental Optometry, Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Hong Kong, Hong Kong Special Administrative Region of China.

Investigative Ophthalmology & Visual Science

|January 1, 2016

Abstract

Purpose:

Apolipoprotein A1 (ApoA1) has been shown to inhibit myopia development in chicks, but the underlying biological mechanism remains unknown. Because ApoA1 interacts with cyclic adenosine monophosphate (cAMP) in many cellular systems, we examined whether this interaction is important in myopia development.

Methods:

The nonmetabolizable cAMP analogue 8-Bromo-cAMP (8-Br-cAMP) was administered intravitreally to the right eyes of 8-day old chicks for 4 consecutive days. Control eyes received vehicle. Chicks in group 1 received 8-Br-cAMP (0.1 mM or 1 mM) and were fitted with -10 diopter (D) lenses on both eyes, whereas chicks in group 2 (0.1 mM 8-Br-cAMP) wore plano lenses over both eyes. The levels of retinal cAMP and ApoA1 were examined in another two groups of chicks wearing -10 D (group 3) and +10 D lenses (group 4) over their right eyes for 3 days, respectively (plano over left eyes).

Results:

The 8-Br-cAMP significantly inhibited development of lens-induced myopia (group 1: 0.1 mM versus vehicle: +1.71 ± 1.22 D versus -8.00 ± 2.19 D; 1 mM versus vehicle: +1.38 ± 1.34 D versus -9.96 ± 1.14 D, mean ± SEM, P < 0.01 for both); 1 mM, but not 0.1 mM 8-Br-cAMP increased expression of retinal ApoA1 levels in right eyes (P < 0.01). The 8-Br-cAMP had minimal effect on normal eye growth. Both retinal cAMP and ApoA1 levels were significantly increased only in hyperopic eyes (group 4).

Conclusions:

The 8-Br-cAMP robustly inhibited development of lens-induced myopia. The increase in retinal ApoA1 observed in cAMP-treated and hyperopic eyes suggested a possible interplay between ApoA1 and cAMP in regulating eye growth.

Insights

Cyclic adenosine monophosphate (cAMP) analogue 8-Bromo-cAMP inhibited myopia development in chicks. Increased retinal ApoA1 in treated and hyperopic eyes suggests a link between ApoA1 and cAMP in eye growth regulation.

Area of Science:

Ophthalmology
Molecular Biology
Developmental Biology

Background:

Apolipoprotein A1 (ApoA1) is known to inhibit myopia development.
The mechanism by which ApoA1 influences myopia is not fully understood.
ApoA1 interacts with cyclic adenosine monophosphate (cAMP) in various cellular contexts.

Purpose of the Study:

To investigate the potential role of the ApoA1-cAMP interaction in the development of myopia.
To determine if modulating cAMP levels affects myopia progression and ApoA1 expression in the retina.

Main Methods:

Chicks received intravitreal injections of 8-Bromo-cAMP (8-Br-cAMP), a nonmetabolizable cAMP analogue.
Lens-induced myopia was created using -10 diopter lenses.
Retinal levels of cAMP and ApoA1 were measured in chicks exposed to myopic, hyperopic, or plano lenses with or without 8-Br-cAMP treatment.

Main Results:

8-Br-cAMP significantly inhibited the development of lens-induced myopia.
A higher concentration of 8-Br-cAMP (1 mM) increased retinal ApoA1 expression.
Elevated retinal cAMP and ApoA1 levels were observed specifically in hyperopic eyes.

Conclusions:

8-Bromo-cAMP effectively prevents myopia development in a chick model.
The findings suggest a significant interplay between ApoA1 and cAMP in the regulation of eye growth.
This interaction may represent a novel therapeutic target for myopia control.

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