Diabetic retinopathy (disturbed function of the eye retina and choroid)

Diabetes is a group of metabolic diseases which manifest themselves in an increased blood glucose level (hyperglycaemia) and stem from decreased secretion or impaired action of insulin. Prolonged hyperglycaemia leads to many pathological changes in internal organs, and in particular in the eyes, kidneys, heart and blood vessels.

In general, 2 basic types of diabetes can be differentiated: type 1 diabetes, related to the disturbed insulin secretion, and type 2 diabetes, occurring as a result of the body’s lowered sensitivity to insulin.

The World Health Organization (WHO) estimates that 4% of the global population suffers from diabetes, i.e. around 135 million people. It is expected that the number of diabetics will increase very sharply in the coming years, reaching the level of around 300 million people in 2025. In Poland, the incidence of diabetes amounts to 5-10% in the population of people over 40.

Diabetes is one of the most frequent causes of significant vision impairment or blindness. Diabetes-related lesions in the eye concern many structures, but the most dangerous ones are the lesions located within the eye retina, defined as diabetic retinopathy. Incidence of diabetic retinopathy increases with the duration of the diseases and the patient’s age, and depends on the type of diabetes.

In type 1 diabetes, the occurrence of diabetic retinopathy is related to the duration of the disease and amounts to 25%, 60%, and 80% of patients 5, 10, and 15 years from the onset of the disease respectively.

In patients with type 2 diabetes, diabetic retinopathy develops in 40% of insulin-treated patients within 5 years from the onset of the disease.

The mechanism behind the development of diabetic retinopathy is very complex and involves the occurrence of numerous pathological biochemical processes in the retina and choroid. These processes include, inter alia, the deposition of sorbitol in the cells, oxidative stress, activation of the C-kinase enzyme and increased production of the vascular growth stimulating factors or the so called angiogenic factors.

In general, pathological processes related to diabetic retinopathy can be divided into pathological changes of the retinal microcirculation, lesions developing in the retinal nerve cells, and lesions stemming from a chronic inflammatory condition.

Results of scientific research suggest that early vascular lesions in retinal microcirculation involve the atrophy of pericytes, i.e. cells which are located in the walls of the retinal blood vessels, which play an extremely important part in the regulation of blood flow through the vessels and in the protection of the vascular endothelium. Subsequently, as a result of pericyte depletion, vascular basement membrane thickens, leukocyte adhesion increases and chronic inflammatory state sets in. The condition is accompanied by the damage of vascular endothelial cells, increase in the permeability of the blood vessel walls, and impairment of the blood-retinal barrier. The damaged vessels undergo deformations, their walls swell and microaneurysms are formed. The weakened blood vessel walls rupture, which leads to microhaemorrhages. Retinal areas covered by microhaemorrhages lose their function, which is manifested in deteriorated vision. The above mentioned lesions are characteristic for the most frequent form of diabetic retinopathy, the so called non-proliferative retinopathy, which occurs in ca. 90% of patients suffering from diabetic retinopathy.

The proliferative type of retinopathy develops in ca. 10% of patients suffering from diabetic retinopathy. Proliferative retinopathy involves processes related to the development of new pathological blood vessels in the retina. Diabetes-related loss of pericytes makes vascular endothelial cells more prone to injury. The bigger blood vessels, devoid of the endothelium, shrink, leading to tissue hypoxia. In reaction to the hypoxia, the secretion of vascular growth factors, i.e. the factors stimulating the development of new blood vessels (angiogenic factors), increases significantly. Currently, there are several such factors that are known us, the best known of which is the so called vascular endothelial growth factor (VEGF). The newly generated blood vessels proliferate in the retina and may also grow into the vitreous body. Their walls are permeable and brittle, and they rupture easily. Depending on the location of the ruptures, blood escapes to the vitreous body (vitreous haemorrhages) or under the retina, which may lead to its detachment. The extravasated blood causes chronic inflammatory states, which deepen the pathological changes within the retina, leading to a considerable vision impairment.

It appears that in diabetes, apart from the vascular lesions, pathological biochemical processes develop within the retinal nerve cells, particularly the bipolar cells. The processes are not directly dependant on the vascular lesions. Genes responsible for the initiation of lytic enzymes, leading to cellular lysis, are activated in the nerve cells. The phenomenon of such a programmed cell death is called apoptosis.

The chronic inflammatory state related to both forms of diabetic retinopathy is probably rooted in the haematological changes within the retinal microcirculation and in the processes initiated by the microhaemorrhages. The processes are associated with increased generation of free radicals, which additionally damage the neighbouring tissues, and first and foremost the retina.

Due to the high complexity of the pathological processes developing within the diabetic eye tissues, treatment of diabetic retinopathy is quite complicated. It includes systemic treatment, consisting in the maintenance of appropriate blood glucose by means of insulin use or special diet, as well as preventive measures and treatment of the lesions developing within the retina and retinal microcirculation.

Recent research shows very beneficial properties of the alpha-lipoic acid (ALA) in the treatment of diabetic retinopathy.

Experimental research has shown that the alpha-lipoic acid has multiple properties contributing to the inhibition of pathological processes within the retina and other tissues in diabetic patients.

The alpha-lipoic acid protects pericytes and inhibits the pathological processes responsible for their damage.

The alpha-lipoic acid also inhibits the generation of angiogenic factors, such as VEGF, which is why it inhibits the process of proliferation of pathological blood vessels. It also manifests antiapoptotic properties and prevents the activation of processes related to the programmed retinal nerve cell death.

The alpha-lipoic acid is also a very potent antioxidant preventing the harmful activity of free radicals in the course of the diabetic retinopathy-related chronic inflammatory state.

Moreover, experimental research has shown that vitamin B1 derivative combined with the alpha-lipoic acid inhibits the development of diabetic retinopathy.

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