Project Details
Projekt
Bilateral cataract following unilateral exposure to ultraviolet radiation. Ocular immune cross-talk and immunmodulation between left and right eye.
Subject Area
Ophthalmology
Term
from 2014 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 261319924
Cataract still is the leading cause of blindness worldwide. Oxidative stress, as provoked from exposure to ultraviolet radiation type B (UVR - B), is today held one of the main factors inducing age-related cataract in humans and animals. Furthermore it is well established that exposure of the skin to UVR-B induces not only tanning and sunburn but also modulates local and systemic immunity leading to immunosuppression via neuropeptide signaling. Recently it has been shown that the ocular immune privilege is altered also in the contralateral eye following unilateral retinal laser burn via a neuropeptide dependent pathway. In previous UVR-B- irradiation studies we found, as an unexpected finding, that after exposure of only one eye also the untreated, contralateral eye undergoes a loss of transparency in the lens. We postulate that the identified neuropeptide substance P via so far unknown cellular and humoral pathways induces the contralateral reaction we observed in the lens. The identification of an ocular immune cross talk between right and left eye and the development of therapies is of high clinical relevance. A similar, so far unexplained contralateral effect after damage to one eye occurs in sympathetic ophthalmitis, a prototypical autoimmune disease in which injury to one eye causes sight-threatening inflammation in the otherwise normal contralateral eye. To test our hypothesis, C57Bl/6 mice will be irradiated unilaterally with UVR-B. Cataract development will be quantified and exposed as well as contralateral eyes will be analyzed for presence of substance P. Furthermore we will concentrate on therapeutic strategies to treat substance P mediated contralateral eye disease. Here the focus lies on possible blocking of substance P signaling pathways with spantide I and II (substance P receptor antagonist) but more importantly we will test substances in our in vivo model that are approved in human therapy and widely used in clinical practice for other indications such as indomethacin, bevacizumab and the substance P receptor antagonists aprepitant and netupitant. Of advantage could be the possibility of a fast transfer of these therapies to the human situation. Thus we anticipate that the characterization of neuropeptide signaling pathways between the eyes and the identification of possible treatment options could allow for promising new strategies to fight numerous eye diseases.
DFG Programme
Research Grants
