Citicoline retards myopia progression following form deprivation in guinea pigs

Abstract

The retinal dopaminergic system is involved in the myopic shift following form deprivation. Citicoline has been demonstrated to stimulate the dopaminergic system in the brain and retina. Furthermore, citicoline has been used in many neurogenic diseases, such as senile cognitive impairment, stroke and Parkinson's disease as well as in amblyopia and glaucoma. Our aim was to investigate the effect of citicoline on the refractive state and retinal dopamine level in form deprivation myopia of guinea pigs. Guinea pigs, at an age of four weeks, were randomly divided into normal control, deprivation, deprived + citicoline and deprived + vehicle groups. Form deprivation myopia was induced by a translucent eye shield covering the right eye. Citicoline was injected intraperitoneally twice a day (500 mg/kg, 9 am and 9 pm) for 10 days. In vitro, retinal explants were cultured with citicoline for 24 h, with a final citicoline concentration of 100 µmol/L. The ocular refractive parameters and retinal dopamine content were measured. After occlusion for 10 days, the form-deprived eyes became myopic with an increase in axial length and a decrease in retinal dopamine content. The intraperitoneal injection of citicoline reduced the myopic degree (from -3.25 ± 0.77D to -0.62 ± 0.47D, P < 0.001) and partially raised retinal dopamine levels (from 0.55 ± 0.21 ng to 0.81 ± 0.24 ng, P < 0.01) in the form-deprived eyes. After 24 h of culturing retinal explants with citicoline, retinal dopamine content increased significantly (from 0.42 ± 0.14 ng to 0.62 ± 0.21 ng, P < 0.05). These results demonstrated that an intraperitoneal injection of citicoline could retard the myopic shift induced by form deprivation in guinea pigs, which was mediated by an increase in the retinal dopamine levels.

Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia

“…The findings of the present study, which are supported by observations made in a previous investigation, may suggest that EGF and members of the EGFR family, such as amphiregulin, are some of the substances that were positively or negatively associated with the development of experimental myopia in previous studies. These substances include dopamine, acetylcholine, and other molecules from the cholinergic system and GABAergic system, insulin, glucagon, glucagon‐like peptide‐1, basic fibroblast growth factor, transforming growth factor beta, vasoactive intestinal polypeptide, retinoic acid, nitric oxide, and sonic hedgehog as well as molecules derived from genes like the FBJ osteosarcoma oncogene and immediate early genes 14‐35 . Experimental investigations and clinical randomized trials have shown that atropine eye drops applied in low concentrations reduce the rate of myopization 35 .…”

Citicoline in the Treatment of Cognitive Impairment

“…It has been demonstrated that citicoline significantly increased dopamine levels and synthesis rate in the striate Effects on the levels of other neurotransmitters have been reported by other authors [174][175][176][177][178]. The action of citicoline upon the dopaminergic system has also been studied by investigating its pharmacological actions in many experimental models [179][180][181][182][183][184][185][186][187][188][189][190][191][192][193]. Citicoline increases norepinephrine release [194], influences the relationship between glutamate and GABA [195], and increases the levels of vasopressin [196] and other pituitary hormones [197,198].…”

Role of Citicoline for Management of Myopic Amblyopia Patients in Teriary Care Hospital of India

“…However, study published by Junfeng Mao et al showed that intraperitoneal injection of citicoline retarded the myopic shift induced by form deprivation in guinea pigs. 2 Another study published by Prachee Vasant Pawar et al showed that improvement in visual acuity with citicoline along with patching was significantly more than that with patching alone, in one year of treatment of amblyopia. 6 Many studies have shown neuro-protective effects of citicoline in glaucoma, amblyopia, non arteritic ischemic optic neuropathy, cerebral stroke, dementia, Parkinson's disease and many other diseases due to increase in dopamine levels in brain and protective effects of phosphatidylcholine in retinal as well as nerve ganglion cells.…”

“…Chronic citicoline treatment leads to increase in dopamine receptor densities and promotes partial recovery of dopamine receptor functions (which normally decreases with aging). 2,3 Citicoline activates the biosynthesis of structural phospholipids (phosphatidylcholine) in neuronal cell membranes, thus an increased neurotransmitter levels and enhanced neuroprotection. 3,4 It stimulates glutathione synthesis and facilitates preservation of sphingomyelin, thus promoting signal transduction in nerve cells of retina.…”

“…5 It reduces retinal nerve fibre layer (RNFL) damage by reducing Nitric Oxide synthase levels and attenuates Nitric Oxide function in the neurons of retina and spinal cord. 2 In the current study, we aimed to study the effects of oral citicoline as a treatment option in myopic amblyopia by looking at the progression, arrest or regression of myopia.…”