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

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.

Characterisation of Cl⁻ transporter and channels in experimentally induced myopic chick eyes.

BACKGROUND: Experimental evidence has shown that myopic and hyperopic optical defocus induces thickening and thinning of the choroids, respectively, moving the retina forward and backward toward the plane of focus; however, the underlying mechanism of this phenomenon remains elusive. It has been hypothesised that the change in choroidal thickness might be elicited by the alteration of ion and fluid transport across the retinal pigment epithelium (RPE). Therefore, the aims of the present study were to determine the content of specific Cl(-) transporter/channel mRNA and proteins in chick RPE in a normal, untreated state and in lens-induced myopia. METHODS: Thirty-five White Leghorn chicks were used. Lens-induced myopia was achieved by securing a -10 D lens in one eye, while the control eye was mounted with a plano lens. The mRNA and protein expression of the targeted Cl(-) transporter and channels were assessed by real-time polymerase chain reaction and western blot, respectively. RESULTS: Our results showed that the gene and protein products of several Cl(-) transporter and channels including NKCC, CFTR, ClC-2, ClC-5, ClC-7 and CLCA were expressed in young chick RPE. After one day of -10 D lens wear, in addition to the myopic shift in refraction and choroidal thinning, there was a parallel reduction in content of some mRNAs and proteins (for example, NKCC) in the myopic eye compared with the fellow eye. Spontaneous recovery of these mRNAs and proteins to control levels was demonstrated after four days of treatment. CONCLUSION: The relative reduction of Cl(-) transporter and channel expression in the myopic eye might cause a decrease in ion and fluid transport across the RPE, leading to a thinning of the choroid and potentially accelerating axial elongation. Understanding of the identity of the Cl(-) transport machinery used in developing lens-induced myopia might facilitate development of novel approaches for controlling myopic progression by influencing fluid transport by the RPE.

Growth-differentiation factor-8 (GDF-8) in the uterus: its identification and functional significance in the golden hamster.

Transforming growth factor-beta superfamily regulates many aspects of reproduction in the female. We identified a novel member of this family, growth-differentiation factor 8 (GDF-8) in the 72 h post coital uterine fluid of the golden hamster by proteomic techniques. Uterine GDF-8 mRNA decreased as pregnancy progressed while its active protein peaked at 72 h post coitus (hpc) and thereafter stayed at a lower level. At 72 hpc, the GDF-8 transcript was localized to the endometrial epithelium while its protein accumulated in the stroma. Exogenous GDF-8 slowed down proliferation of primary cultures of uterine smooth muscle cells (SMC) and endometrial epithelial cells (EEC). In addition, GDF-8 attenuated the release of LIF (leukaemia inhibiting factor) by EEC. As for the embryo in culture, GDF-8 promoted proliferation of the trophotoderm (TM) and hatching but discouraged attachment. Our study suggests that GDF-8 could regulate the behavior of preimplantation embryos and fine-tune the physiology of uterine environment during pregnancy.

Absence of paternal accessory sex glands dysregulates preimplantation embryo cell cycle and causes early oviductal-uterine transit in the golden hamster in vivo.

We hypothesize that deletion of paternal accessory sex glands compromised developmental potential of preimplantation embryos because of dysregulation of blastomeric cell cycle regulators. Quantification by immunocytochemistry showed disrupted cyclicity of proliferating cell nuclear antigen, augmented p53 and p21 expression, and premature transit from oviduct to uterus.