Ageing and oxidative stress in ocular surface diseases

What are the eye diseases whose onset and progression can be associated with oxidative stress? Is there any difference in the 'trigger' mechanism in the various cases?
Many eye diseases are linked to oxidative stress; for example, Age-Related Macular Degeneration (AMD) is considered to be caused by oxidative stress, just as smoking, exposure to blue and ultraviolet light and a high-fat diet are causes of oxidative stress that results in AMD. Cataracts are also considered to be caused by oxidative stress as UV radiation and vitamin C deficiency are considered causative factors. As far as the ocular surface is concerned, pterygium and conjunctivocalasis are pathologies related to oxidative stress.

In the pathogenesis of dry eye, inflammation plays a key role in the mechanism of ocular surface damage. Could you clarify the complex interaction between inflammation and oxidative stress: what is the cause and what is the effect?
The initial mechanism is believed to be the same, namely the aggression of important molecules in the cells of each tissue, but as tissues vary, the result (in terms of pathology) is different.

The ocular surface is particularly exposed to environmental agents, is this relevant to oxidative stress-induced damage?
Yes, this is very important. The ocular surface is exposed to air when the eye is open, whereas when the eyes are closed and during sleep, the eye is not exposed to air so that the oxygen level varies from 150 mmHg to 55 mmHg. It is believed that it is precisely oxygen reperfusion that induces the formation of many free radicals. And it is not just oxygen, as the ocular surface is exposed to ultraviolet light, which causes considerable oxidative stress.
In addition, many of the chemicals that are suspended in the air, such as smoke, produce free radicals on the ocular surface that result in severe inflammation.

Is there a relationship between cigarette smoking and oxidative stress in the dry eye?
Yes, cigarette smoking increases the effects of oxidative stress in the dry eye. My research group has developed several models on smoking and dry eye that show an extremely negative effect.

Apart from future treatments aimed at the therapeutic inhibition of oxidative stress, is there a rationale for calorie reduction aimed at preventing the decline in lacrimal gland function and morphological changes associated with oxidative stress?
Yes, and it is an important question. A recent review by Verdin's research group identifies calorie restriction as the main intervention to be considered for an anti-ageing approach. The 'effector phase' of calorie restriction appears to be the control of mitochondrial oxidative damage. Control of oxidative stress can be achieved either directly or by reducing calorie intake, which determines mitochondrial oxidative stress.

You are among the authors of a study recently published in Investigative Ophthalmology and Visual Science (Jan. 2013) on lipid oxidative stress in Sjögren's syndrome patients. What are the most important findings reported in this study?
Sjögren's syndrome is an autoimmune disease of an inflammatory nature, so inflammation is the central element of this pathology. However, in this study we were able to show that oxidative stress is also very high and therefore there is a possibility that the vicious circle between oxidative stress and inflammation is established in the progression of the disease.
Therefore, not only controlling inflammation, but also controlling oxidative stress can be a good strategy for treating Sjögren's syndrome.
In summary, oxidative stress is related to the ageing process itself and also, locally, to the eye, especially the ocular surface, when exposed to the environment, oxygen reperfusion, UV radiation, blue light, smog, smoke, numerous pathogens as well as contact lens wear. Tissues are continuously attacked by oxidative stress and although the system is strong in counteracting oxidative stress, when the balance of the system is altered, a pathological condition results that can be treated through oxidative stress control.

Kazuo Tsubota

To get in touch with Prof. Tsubota write to Catherine Oshima E-mail: catherine@z8.keio.jp

Prof Kazuo Tsubota
Head of the Department of Ophthalmology at Keio University School of Medicine (Tokyo, Japan) and Visiting Professor at the Department of Ophthalmology at Tokyo Dental College Ichikawa General Hospital (Chiba, Japan). Prof. Kazuo Tsubota is an internationally recognised dry eye expert who has been interested in the pathogenesis and treatment of this disease. He currently leads many research projects dealing with ageing processes, ocular surface reconstruction, corneal regeneration, the lacrimal gland, the immunology of Sjögren's syndrome and wound healing after refractive surgery.

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