Studies on the interactions of retinal dopamine with choroidal thickness in the chicken

Abstract

Purpose Recently, an increasing number of studies relied on the assumption that visually induced changes in choroidal thickness can serve as a proxy to predict future axial eye growth. The retinal signals controlling choroidal thickness are, however, not well defined. We have studied the potential roles of dopamine, released from the retina, in the choroidal response in the chicken. Methods Changes in retinal dopamine release and choroidal thickness changes were induced by intravitreal injections of either atropine (250 µg or 360 nMol), atropine combined with a dopamine antagonist, spiperone (500 µMol), or spiperone alone and were tracked by optical coherence tomography (OCT). To visually stimulate dopamine release, other chicks were exposed to flicker light of 1, 10, or 400 Hz (duty cycle 0.2) and choroidal thickness was tracked. In all experiments, dopamine and 3,4-Dihydroxyphenylacetic acid (DOPAC) were measured in vitreous, retina, and choroid by high-performance liquid chromatography with electrochemical detection (HLPC-ED). The distribution of the rate-limiting enzyme of dopamine synthesis, tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor (VEGF), and alpha2A adrenoreceptors (alpha2A-ADR) was studied in the choroid by immunofluorescence. Results The choroid thickened strongly in atropine-injected eyes, less so in atropine + spiperone–injected eyes and became thinner over the day in spiperone alone-, vehicle-, or non-injected eyes. Flickering light at 20 lx, both 1 and 10 Hz, prevented diurnal choroidal thinning, compared to 400 Hz, and stimulated retinal dopamine release. Correlation analysis showed that the higher retinal dopamine levels or release, the thicker became the choroid. TH-, nNOS-, VEGF-, and alpha2A adrenoreceptor–positive nerve fibers were localized in the choroid around lacunae and in the walls of blood vessels with colocalization of TH and nNOS, and TH and VEGF. Conclusions Retinal DOPAC and dopamine levels were positively correlated with choroidal thickness. TH-positive nerve fibers in the choroid were closely associated with peptides known to play a role in myopia development. Findings are in line with the hypothesis that dopamine is related to retinal signals controlling choroidal thickness.

GABAB Receptor Activation Affects Eye Growth in Chickens with Visually Induced Refractive Errors

“…We can therefore only speculate if the effect is a direct receptor-mediated effect in this tissue, or an indirect effect. An indirect effect of baclofen mediated solely by changes in dopamine metabolism can be excluded, since it was shown that retinal dopamine and DOPAC levels are positively correlated with ChT in the open eyes of chickens [ 57 ] but not in ametropic eyes, as indicated by lower retinal dopamine metabolism and higher ChT in LIH eyes.…”

Relationship Between Autonomic Nervous System Activity and Axial Length in Children

“…Choroidal blood flow and CT are regulated by the autonomic nervous system (sympathetic nervous stimulation causes a substantial reduction in choroidal blood flow and CT [31,[63][64][65][66], and the parasympathetic input to the choroid has a vasodilation effect and serves to increase choroidal blood flow and CT [31,32,67,68]). The intrinsic rhythm of the choroid is also influenced by the autonomic nervous system (the choroid possesses a network of intrinsic choroidal neurons that lie in the choroidal stroma [12,32,69], and these intrinsic choroidal neurons appear to receive both sympathetic and parasympathetic input, suggesting they are controlled by the autonomic nervous system [70,71]). In addition, the choroid can release certain autonomic neurotransmitters (eg, vasoactive intestinal peptide, nitric oxide) [12,24,31,71] and change the permeability of the choroid, making the growth factor released by the choroid more easily arrive at the sclera, and further remodel the scleral extracellular matrix [11,61,72,73].…”

“…The intrinsic rhythm of the choroid is also influenced by the autonomic nervous system (the choroid possesses a network of intrinsic choroidal neurons that lie in the choroidal stroma [ 12 , 32 , 69 ], and these intrinsic choroidal neurons appear to receive both sympathetic and parasympathetic input, suggesting they are controlled by the autonomic nervous system [ 70 , 71 ]). In addition, the choroid can release certain autonomic neurotransmitters (eg, vasoactive intestinal peptide, nitric oxide) [ 12 , 24 , 31 , 71 ] and change the permeability of the choroid, making the growth factor released by the choroid more easily arrive at the sclera, and further remodel the scleral extracellular matrix [ 11 , 61 , 72 , 73 ]. Thus, changes in autonomic nervous system activity in myopia may accelerate the progression of axial elongation and myopia by regulating the choroid and sclera.…”

Short‐term effects of cyclopentolate and tropicamide eye drops on macular choroidal thickness in myopic children

“…As a result, they may modulate changes in ChT by causing fluid efflux within the choroid, leading to its thinning. 33,35,36 Atropine (also an anti-muscarinic agent) has been shown to increase ChT, potentially through nitric oxide 37 or dopamine 38 pathways. Cyclopentolate may affect the same pharmacological mechanisms, but analysis of the short-term ChT changes within the atropine and placebo groups showed that post-cyclopentolate choroidal thinning did not differ significantly between the atropine and placebo groups.…”