Ageing as a preclinical condition of ocular surface diseases: a new perspective based on the concept of 'parainflammation'.
The ocular surface, like every part of our organism, evolves and transforms as we age. Ageing is actually a very complex process and the progress of scientific research allows us to understand many of its physiopathological aspects better and better.
In recent years one hears more and more about InflammAgingespecially with reference to certain chronic diseases. As can be guessed from the word itself, composed of 'Inflamm' and 'Aging', the term refers to a chronic, asymptomatic, low-grade inflammation that arises, in the absence of infection, in old age.
InflammAging probably has multiple, often concomitant causes, among which one can enumerate:
- the accumulation of altered molecules (microRNA, mitochondrial DNA or histones) released by damaged cells. These molecules are recognised by the cells of the immune system, resulting in the activation and development of inflammation;
- the increase in the number of senescent cells, which release a mix of pro-inflammatory substances into the blood;
- persistent viral infections, such as cytomegalovirus;
- alteration of the gut microbiota;
- high-calorie diets;
- chronic stress condition.
On a systemic level, inflammAging, as a chronic inflammatory state, has detrimental effects on health and contributes to biological ageing and the development of many age-related diseases.
This process also occurs in the eye and particularly in the ocular surface. It is necessary at this point to premise that the ocular surface is a complex morpho-functional unit, in which multiple anatomical and cellular components (cornea, conjunctiva, lacrimal glands, Meibomian glands, tear film, immune cells and nerve fibres) cooperate to maintain homeostatic balance. This balance is the condition for the reparative processes to take place that heal the daily micro-damage to the surface itself. At the level of other apparatuses (such as the cardiovascular, endocrine and nervous systems) these innate and self-limiting autoimmune mechanisms that maintain and restore homeostasis have been called "parainflammation'. When parainflammation is dysregulated, it can trigger actual inflammation, which manifests itself with the clinical signs observed in chronic eye diseases, such as Age-Related Macular Degeneration.
InflammAging is, therefore, the chronic, subclinical form of parainflammation that arises with ageing.
Recent studies have shown that the concept of InflammAging can be extended to the ocular surface and that even in apparently healthy and asymptomatic subjects, clinical and biomolecular changes can be detected. Particularly with advancing age, a number of conditions arise:
- The stability of the tear film is reduced;
- Tear production decreases;
- OSDI scores increase, particularly in women after menopause
- They increase inflammatory markers (such as ICAM-1, MUC5AC, and IL-8).
These results support the thesis of age-related damage to the ocular surface system and the induction of a persistent InflammAging state.
In summary, these data suggest a different viewpoint for assessing the effects of ageing on the morpho-functional system of the ocular surface. Aging, that is, could be considered not only a risk factor for ocular surface diseases, but in fact a clinical and/or subclinical condition.
The countless research projects currently underway will help shed light on this new perspective, which also shows new horizons for the therapeutic options that can be implemented.
- Di Zazzo A, Micera A, Coassin M;et al. InflammAging at Ocular Surface: Clinical and Biomolecular Analyses in Healthy Volunteers. Investigative Ophthalmology & Visual Science April 2019, Vol.60, 1769-1775. doi:https://doi.org/10.1167/iovs.18-25822
- Franceschi C, Garagnani P, Parini P, et al. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14(10):576-590. doi:10.1038/s41574-018-0059-4
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