Oxidative stress and degenerative eye diseases

Oxidative stress is a phenomenon that contributes to the onset of many degenerative eye diseases. Understanding the mechanism underlying the imbalance between oxidants and antioxidants is crucial to better manage these eye diseases. Oxidative damage occurs both in the components of the anterior segment, such as the cornea and crystalline lens, and the posterior segment, such as the retina, adversely affecting their visual function. Eye diseases associated with this imbalance include cataracts, age-related macular degeneration, keratoconus and glaucoma.

In this article, we examine the mechanisms involved and possible therapeutic strategies to reduce oxidative stress in the eye.

Oxidative stress and ROS

Oxidative stress is one of the fundamental triggers of many eye diseases and develops due to aexcessive production of reactive oxygen species (ROS).

Reactive oxygen species are highly reactive oxygen-containing molecules, which, uncontrolled, can cause cellular damage to lipids, proteins and DNA itself.

Reactive oxygen species are chemical compounds that include both free radicals and non-radical species. Free radicals include:

- Superoxide radical (O₂--)

- Hydroxyl radical (-OH)

Non-radical species include:

- Hydrogen peroxide (H₂O₂)

- Ozone (O₃)

- Oxygen singlet

Reactive oxygen species are mainly formed through cell metabolism itself, particularly in the mitochondria, where oxygen is used to produce energy. During this process, reactions can occur that generate ROS as by-products. External factors such as pollution, UV radiation and certain toxic substances can increase ROS production, leading to an imbalance, known as 'oxidative stress'.

In controlled quantities, ROS play important roles in immune response and cell signalling mechanisms, while their excessive production can cause oxidative damage that impairs cell function. When ROS production exceeds the body's ability to neutralise them, progressive damage occurs that can lead to pathological conditions.

Oxidative Damage in Ocular Structures

The eye is particularly susceptible to oxidative stress, as the ocular surface is directly exposed to light rays, while the posterior part, in particular the retina, has a very intense metabolism, which can lead to an increased production of ROS.

In addition, certain genetic polymorphisms, inflammation and environmental pollution play a significant role in favouring the accumulation of ROS in ocular tissues. These elements may further impair antioxidant defence mechanisms, increasing the risk of ocular diseases.

L'impact of oxidative stress on ocular tissues leads to a series of structural and functional changes, which can result in impaired visual function that, if left unchecked, can lead to low vision and, in severe cases, blindness.

It is therefore crucial to adopt preventive and therapeutic strategies to minimise damage.

Cornea

The cornea is a transparent avascular tissue consisting of three main layers, an outer epithelium, a stroma containing fibroblasts and an inner endothelium. The transparency of the cornea is essential for good quality vision and can be compromised by the accumulation of ROS and oxidative stress.

In the case of the cornea, the source of the oxidative stimulus is mainly solar ultraviolet radiation, as the cornea absorbs on average 92% of the UV-B rays that reach the eye.

Under normal conditions, the cornea is equipped with natural antioxidant systems that include direct free radical scavengers (low molecular weight antioxidants such as vitamin C, vitamin E, beta-carotene, glutathione, ferritin, alpha-tocopherol) and indirect scavengers (catalase, superoxide dismutase, glutathione peroxidase and reductase).

With advancing age, there is a malfunctioning of corneal antioxidant mechanisms, which leads to the accumulation of ROS and oxidative stress damage that plays a crucial role in the development of diseases such as Fuchs' endothelial dystrophy, keratoconus and granular corneal dystrophy type 2.

Crystalline

The crystalline lens is the natural lens of the eye that allows light to be properly focused on the retina and must be transparent to perform its function.

Cataract is a multifactorial disease that leads to opacification of this natural lens and oxidative stress is among the main causative factors of cataractogenesis. Oxidative stress, in fact, damages the proteins of the crystalline lens, causing its opacification.

As ageing progresses, natural antioxidant defences deteriorate and there is a cumulative response to environmental toxic factors that leads to an excessive production of ROS in epithelial cells and superficial fibrous cells of the lens, as well as in the aqueous humour. Exposure to UV radiation leads to oxidative damage through the photochemical production of ROS, incusi superoxide and its derivatives and other potent oxidants such as hydrogen peroxide, hydroxyl radicals and singlet oxygen.

Glaucoma

Glaucoma is a degenerative optic neuropathy, characterised by progressive degeneration of retinal ganglion cells. It is one of the world's leading causes of irreversible blindness and the primary risk factor is identified as elevated intraocular pressure due to abnormal resistance to aqueous humour drainage through the trabecular meshwork. Increased ROS production and oxidative damage to the retina due to the accumulation of free radicals have been identified as concomitant causes of glaucoma onset and progression.

DMLE

Age-related macular degeneration (AMD) is a major cause of low vision and blindness in the over-65 population.

It appears that the excessive production and accumulation of ROS plays a key role in the pathogenesis of AMD and the damage that occurs in photoreceptors and retinal pigment epithelium (EPR) cells in this pathology.

The level of ROS increases in the retina with age, even though both the retina and epithelial cells are rich in both enzymatic and non-enzymatic antioxidants. However, when there is an increased production of ROS and a lowering of natural antioxidant defences, oxidative stress occurs, leading to damage to photoreceptors, EPR cells and the choriocapillaris through a process of apoptosis.

Reactive oxygen species tend to accumulate in the retina, firstly, because the latter is the most oxygen-consuming tissue in the entire human organism, secondly, the ERP and the photoreceptors in the macula are exposed to high-intensity light, and the cell membranes of the photoreceptors are rich in polyunsaturated fatty acids (PUFA) that are rapidly oxidised.

Photoreceptors are cells with high metabolic activity and a high need for oxygen and nutrients, which are absorbed by the blood stream. The oxygen tension in the retina is 70 mmHg. This particular condition favours the genesis of free radicals.

Antioxidant Biomarkers

The eye has antioxidant defence mechanisms to combat oxidative stress. These systems are crucial for maintaining ocular health and preventing degenerative diseases.

Antioxidant biomarkers offer indications of the eye's ability to neutralise ROS and, therefore, measuring these biomarkers can help identify oxidative imbalances, in particular:

• Glutathione: A powerful antioxidant present in eye cells.
• Vitamin C and EEssential for neutralising free radicals.

The analysis of these biomarkers can provide valuable information on ocular health and guide treatment decisions.

Predictive Diagnosis

Le predictive diagnostics are important tools for identifying the risks of eye diseases related to oxidative stress at an early stage. Using advanced technologies, it is possible to monitor eye health and intervene at an early stage.

• Regular ScreeningThey can identify the first signs of oxidative damage.
• Advanced technologiesThey allow an accurate assessment of ROS levels.

By implementing these strategies, one can improve the management of eye diseases and preserve vision.

Natural Antioxidant Therapies

Natural antioxidant therapies offer a promising approach to reducing oxidative stress in the eye. By incorporating antioxidants into the diet, ocular health can be improved.

The therapeutic nutritional approaches include the use of supplements to combat oxidative stress. The supplementation of these substances can complement the active therapies adopted and offer additional benefits.

• Lutein and zeaxanthin supplements
• Fish oil: Rich in omega-3, it helps maintain ocular health.

• Vitamin A: Essential for night vision and retinal health.
• FlavonoidsThey protect eye cells from free radical damage.

Supplementing these antioxidants in the diet can offer natural and sustainable protection for the eyes, reducing the risk of oxidative stress-related diseases.

Nita M, Grzybowski A. The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults. Oxid Med Cell Longev. 2016;2016:3164734. doi: 10.1155/2016/3164734.