Unmet NeedAlmost 11 million people in the United States have symptoms of age-related macular degeneration (AMD). AMD is a multifactorial disease distinguished by progressive degeneration in the macular region of the eye, resulting in irreversible central vision loss among the elderly population. Current evidence suggests that inflammation plays a vital role the pathogenesis of AMD. Mast cells (MCs) are key effector cells of inflammation and play an important role in autoimmunity. MCs are widely distributed in connective tissue and mucosa and are frequently found in close proximity to blood vessels. MCs also play a key role in inflammation in other tissues like skin and conjunctiva, and thus, may play a role in choroidal inflammation as well. MCs have the ability to induce angiogenesis, and it has been demonstrated that they are present around Bruch’s membrane during both the early and late stages of both choroidal neovascularization (CNV) in AMD and geographic atrophy (dry AMD). The current, supported hypothesis is that when MCs go through degranulation (DG), AMD starts to progress. Thus, in order to halt progression of AMD, MC DG must be halted. There are many drugs on the market attempting to halt the progression of MC DG and AMD. However, current efficacy tests for these drugs can take 6-10 weeks. Thus, there is a need for a faster assay to test MC DG drugs.
Technology OverviewThe inventors have created an ex-vivo model for the rapid evaluation of choroidal mast cell degranulation. This assay provides drug evaluation in 180 min as opposed to 6-10 weeks, which is required with current in vivo model readouts. This assay allows the effect of drug on MC DG as well as macrophage activation to be assessed rapidly. The route of administration for a drug can also be tested rapidly. Animals receive drugs for 5 days via different routes of administration. Then, the effectiveness of the route of administration and the drug can be evaluated by using the eye cups from the dosed animals in the assay. The inventors have tested the assay, finding that in their particular tests, MC quiescence through drugs prevented activation of macrophages, indicating that MC cytokine release was prevented. The ex-vivo model system will provide new opportunities for rapid screening of drugs targeting MCs and subsequent ocular inflammation, which MCs stimulate.
Stage of DevelopmentThe assay has been tested with selected drugs, and is in further stages of testing for use in screening drugs for AMD.
PublicationScience Advances, submitted
