New therapeutic strategies in the resolution of ocular inflammation

Introduction
The monograph 'Inflammation: clinic and therapy' (Part I and II), published by 'l'Oculista Italiano', brings together numerous relevant scientific contributions highlighting the importance of the inflammatory component in various ocular diseases.
The two volumes describe for each pathology the current pharmacological, preventive and/or curative treatment for the therapeutic resolution of inflammation involving both the anterior and posterior segments of the eye. The efficient resolution of the inflammatory response is indicated by the successful outcome of the treatment as reflected by the protective effect of the compromised tissue, the removal of debris and dead cells and the return of damaged tissue to homeostasis (Fig. 1).

Fig. 1. Multistep process in the resolution of inflammation. Modified by: Recchiuti A. Resolvin D1 and its GPCRs in resolution circuits of inflammation. Prostaglandins & Other Lipid Mediators. 2013;107: 64-76. Legend: PMN: Polymorphonuclear leukocytes; M: Macrophage; MP: Plasma microparticles.
Fig. 1. Multistep process in the resolution of inflammation. Modified by: Recchiuti A. Resolvin D1 and its GPCRs in resolution circuits of inflammation. Prostaglandins & Other Lipid Mediators. 2013;107: 64-76. Legend: PMN: Polymorphonuclear leukocytes; M: Macrophage; MP: Plasma microparticles.

It has been further confirmed how the inflammatory process involves a complex cascade of molecular and cellular biological signals, that alter the physiological responses of the ocular tissue concerned.
The monograph also clearly shows how phlogosis is a transversal process which, when triggered by an injury event, results in particular clinical symptoms, not only confined to ocular pathologies frequently associated with inflammatory processes (e.g. allergy, conjunctivitis, keratitis, uveitis, etc.), but also, as has been demonstrated in recent years, to pathologies such as glaucoma, AMD and diabetic retinopathy.
New revisions emerge from the monograph by several authors also on the inflammatory aspects related to ocular surgery e on restoring tissue function. At the site of the lesion, cells release molecular signals that cause a number of changes in the affected area: dilation of blood vessels, increased blood flow and vascular permeability, exudation of fluids containing proteins such as immunoglobulins, and invasion by leucocytes. Several types of leucocytes, including granulocytes, monocytes and lymphocytes, are involved in the inflammatory process.
Continuing progress in the knowledge of the biochemical and cellular pathways associated with the inflammatory response has made it possible to enter the innermost mechanisms of ocular pathologies. The clinician thus has the possibility of using not only drugs that have already been clinically tested and consolidated (corticosteroids, non-steroidal anti-inflammatory drugs, anti-proliferative agents, anti-suppressants, biopharmaceuticals), but also of testing new pharmacological hypotheses for some more complex ocular pathologies thanks to which, also with the support of new drug administration methods, it is now possible to manage many ocular inflammatory processes of the anterior segment (e.g. dry eye, keratitis, conjunctivitis) and also of the ocular segment of the eye with sufficient efficacy. dry eye, keratitis, conjunctivitis) and also in the posterior segment of the eye (e.g. diabetic macular oedema, uveitis). However, although a broad therapeutic armamentarium is available, for some ocular pathological conditions, especially those characterised by high chronicity, the use of certain drugs poses problems of efficacy and/or toxicity. Chronic and prolonged inflammation is a defining feature of diseases such as atherosclerosis, obesity, diabetes, rheumatoid arthritis, asthma and various types of cancer. Many of these diseases have now established ocular manifestations in diabetic retinopathy, scleritis, uveitis, dry eye syndrome and ocular neoplasms. This also leads us to take a close look at the pharmacological and clinical advances that are being made in areas seemingly distant from ophthalmic application, but which could potentially, by translation, also be usable in the ocular field. Indeed, despite the fact that many ocular tissues have an immuno-privileged or highly evolved system to protect the delicate visual axis1-3 the essential control of acute inflammation is regulated by the same general pathways, mediators and effector cells that manage inflammatory responses in other organs. It is no coincidence that most of the immunosuppressants used in inflammatory eye diseases were originally developed in transplant medicine, for rheumatic diseases or other systemic diseases of inflammatory origin.
Recently, a significant alteration in the cytokine and chemokine profile was observed in aqueous humour samples from diabetic patients without any overt retinal pathology, but with a marked similarity to what was found in patients with overt retinopathy4. This scientific information not only lends further support to the fact that chronic inflammation plays a significant role in the pathogenesis of retinopathy, but also suggests that the inflammatory process is activated even before retinopathy (diabetic and/or proliferative) is clinically diagnosed. The alteration in the profile of certain cytokines could, therefore, become both a predictive marker, but also an important target for the development of future therapeutic options. In addition, the considerations described so far reinforce the hypothesis that although the current therapeutic armamentarium allows for the effective management of the inflammatory component of many ocular pathologies, the patient's demand for new diagnostic tests, new more effective and/or safer drugs still has ample experimental margins to be satisfied. In the remainder of this article, some hints on the pharmacology of inflammation will be taken up to point out some examples of the development of potential new therapeutic approaches that could, in the near future, prove to be alternative and/or complementary to those currently in use.

Leggi tutto

Dr. Carmelo Chines
Direttore responsabile

 C'è molto di più per te se ti iscrivi qui

Mandaci i tuoi commenti, le tue richieste e le tue proposte per arricchire i contenuti del nostro portale.

    This site is protected by reCAPTCHA. The conditions of use indicated in the Privacy Policy.