Ocular neurodegenerative diseases such as glaucoma, the diabetic retinopathy and age-related macular degeneration are common pathological conditions responsible for the development of blindness in the working-age and elderly population in developed countries. Indeed, in these diseases a neurodegenerative process is triggered that causes irreversible damage to the retina and leads to progressive vision loss.
Many of the therapies currently used for these diseases fail to halt or totally slow down disease progression. Therefore, some complementary treatments with substances that have neuroprotective properties may help to enable better management of the disease. In particular, citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant and anti-inflammatory properties and their use could have a beneficial effect in the case of neurodegenerative eye diseases.
Citicoline
Cytiocholine (cytidine-5′-diphosphocholine or CDP-choline) is a mononucleotide composed of ribose, cytosine, pyrophosphate and choline. Cytiocholine has pleiotropic properties, as it activates neural metabolism, stabilises the neuronal membrane and promotes neurotransmission. It also contributes to the synthesis of structural phospholipids in cell plasma membranes and acetylcholine, an important neurotransmitter.
If citicoline is taken orally, the compound is hydrolysed to form choline and cytidine, which are used by cells to generate phospholipids; therefore, the administration of citicoline facilitates the exogenous supply of choline and cytidine. Although choline is synthesised endogenously by the body, the amount produced is not sufficient to meet the body's demands and, therefore, it is considered an essential nutrient in animal and human diets. The average recommended intake of choline for adult humans is approximately 550 mg/day for men and 425 mg/day for women, although requirements depend on factors such as age, sex and weight.
For administration, citicoline can be used in the form of free-base citicoline (as a dietary supplement) and citicoline sodium; the latter is mainly used as a drug for the treatment of neurological disorders. Citicoline is currently available both as an intramuscular injection and as an oral formulation and topical solution, to be instilled as eye drops. Studies conducted in the eye have shown improvements in visual function following therapy in patients with glaucoma, diabetic retinopathy, non-arteritic ischaemic optic neuropathy (NAION) and amblyopia.
Coenzyme Q10
Coenzyme Q10 (CoQ10) is a fat-soluble molecule whose molecular structure is similar to that of some vitamins. However, it is not a vitamin, as cells in the human body can synthesise it from scratch. Q10 is also called ubiquinone, due to its ubiquitous presence in virtually all cells of the human body. This molecule consists of a central benzoquinone ring linked to a chain of 10 isoprenoid lipid units. CoQ10 exists in an oxidised (ubiquinone) and reduced (ubiquinol) form and its normal function involves continuous interconversion between these two forms. In addition, there is a third, partially reduced state (ubisemikinone).
CoQ10 is found in the inner mitochondrial membrane, cell membranes and blood, bound to lipoproteins both high and low density. It is involved in numerous biological processes, the most important of which is the synthesis of adenosine triphosphate (ATP). CoQ10 participates in the electron transport chain that takes place during aerobic cellular respiration in the mitochondria, which means it is essential for energy production in cells. The reduced form of CoQ10 (CoQ10H2) acts as a powerful antioxidant and can counteract the effects of free radicals.
Endogenous CoQ10 levels are determined by both the rate of production and the rate of consumption in the body and can be altered in various diseases. Instead, only a small amount of CoQ10 is obtained through the diet. There are three possible causes of CoQ10 deficiency in the body: deficient synthesis, reduced intake or increased utilisation by cells. CoQ10 levels are fairly stable in cells, but concentrations vary between different tissues and organs. Moreover, the amount of CoQ10 decreases with age. The possibility of increasing CoQ10 levels in different organs or tissues through diet and food supplementation has been widely explored in recent decades.
Citicoline and CoQ10 in retinal diseases
Given the characteristics and properties of citicoline and CoQ10, several studies have investigated their efficacy in aiding the treatment of retinal diseases related to neurodegeneration.
For instance, citicoline has neuroprotective properties as it prevents neuronal membrane rupture and apoptosis in neurodegenerative processes. It also plays an antioxidant role in neurodegenerative diseases characterised by oxidative stress, such as glaucoma and ischaemic neuropathies. Studies have shown that both eye drop instillation and oral administration of citicoline produce improvements in visual function. Data supporting the role of citicoline in preventing neurodegeneration in diabetic retinopathy are also available in the literature. In addition, one study also demonstrated a beneficial effect of citicoline in age-related macular degeneration, in relation to which it has an anti-apoptotic and antioxidant effect.
Similar observations have been made for CoQ10, which exhibits antioxidant and anti-apoptotic effects in glaucoma, diabetic retinopathy and age-related macular degeneration, irrespective of the method of administration, either in the form of eye drops or via dietary supplementation.
In essence, the studies conducted so far show that the administration of citicoline and CoQ10 have a promising effect in controlling the progression and promoting the visual function of many retinal diseases. These molecules may, therefore, be useful as adjuvant treatments for various retinal diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration.
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