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A site for sore eyes: New target for allergies found under the eyelid

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14.01.2005

Scientists have found a protein in the eye which plays a critical role in how an allergic response develops over a 24-hour period. The University College London (UCL) team hope their discovery will pave the way for new treatments for allergic diseases such as asthma, eczema and hay fever.

In a study published today in the online edition of the Journal of Clinical Investigation, Professor Santa Jeremy Ono and colleagues from UCL’s Institute of Ophthalmology and Moorfields Eye Hospital found that the macrophage inflammatory protein-1a, known as MIP-1a and located in the eye, plays a crucial role in the early stages of an allergic response. Their findings suggest that drugs that block the binding of MIP-1a to its receptors could help in the treatment of ocular allergy and other allergic diseases.

Allergies affect over one third of individuals in the Western world, with 17 million people in the UK currently suffering from asthma, conjunctivitis, eczema or hay fever.

Allergic responses develop in two phases. The first phase involves an immediate hypersensitivity reaction within one hour of exposure to an allergen, where mast cells (key cells responsible for causing allergies) release histamine and other molecules such as chemokines. MIP-1a is one such chemokine.

The second phase, which occurs 12 to 24 hours after exposure, involves the recruitment of inflammatory cells to the site of inflammation. While the role of chemokines in the second phase is well characterized, little is known about how chemokines contribute to the first phase of an allergic disease.

Ono and colleagues discovered that within the clear membrane that coats the inner surface of the eyelid and outer surface of the eye, known as the conjunctiva, MIP-1a was essential in the initial stages of development of an allergic response.

MIP-1a was also necessary for the second phase of the disease, which is associated with chronic allergy. It is likely that MIP-1a or similar molecules are also essential for the development of other allergies such as asthma, dermatitis or anaphylaxis, a body-wide allergy that left untreated can result in death.

The UCL study suggests that drugs that block the binding of MIP-1a to its receptors CCR1 or CCR5 may have therapeutic value in the treatment of ocular allergy and possibly other allergic diseases.

Professor Ono says: "Current treatments for severe eye allergy are either ineffective or have associated side effects, such as glaucoma and cataract formation, so our study will be of interest to allergists and ophthalmologists. Many current allergy treatments target symptoms rather than the cause of the disease, meaning this discovery could constitute a new target for the treatment of allergic diseases.

"We are currently carrying out studies to test the efficacy of existing drugs that block MIP-1a and similar molecules in the therapy of allergic diseases. Clinical trials are anticipated shortly and if they prove effective, these studies may lead to new therapies within the next 5 to 7 years."

Jenny Gimpel | Source: EurekAlert!
Further information: www.ucl.ac.uk

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