Controlling the influence of macrophages as a novel therapeutic strategy for age related macular degeneration

Prof. Itay Chowers, M.D.

Age related macular degeneration (AMD) is the most common cause of irreversible and legal blindness in the developed world. In the United States alone, nearly two million individuals are afflicted with severe end-stage AMD. Seven million more have early stage AMD and are at high risk of developing advanced AMD. In Israel, the number of AMD patients already exceeds 100,000. As the population ages, the disastrous impact of AMD on society will increase. AMD occurs when a small central portion of the retina known as the macula degenerates. This part of the retina is essential for sharp, detailed central vision. Thus, AMD might interfere with simple every day activities such as seeing faces, driving, reading, writing or performing close work.

There are two sub-types of AMD: the dry (atrophic) type where there is a progressive degeneration of the macula. This form is quite common and about 80% (8 out of 10) people who have AMD have the dry form; unfortunately, there is no current therapy for this type of AMD that is considered to be a precursor for the wet type or second subtype. The next form is the wet (neovascular) subtype which is less common, albeit it bares substantial consequences on vision. Wet AMD occurs when new, abnormal blood vessels grow under the retina. These vessels may leak blood or other fluids, causing scarring of the macula. While both forms of the disease might cause severe visual loss, you lose vision faster with wet AMD than with dry AMD. These two forms of AMD are clinically distinct, so therapy for the wet type will not cure the dry type. Although the wet type is treated with intraocular injections of biological compounds, such therapy is often not sufficient for the long-term, and one fifth of the patients do not enjoy the visual benefits from this therapy.

Prof. Chowers from the Dept. of Ophthalmology at Hadassah Medical Center in Jerusalem, as well as others has demonstrated the importance and role of macrophages in AMD. Macrophages are a sub-population of white blood cells which have been found to be attracted to the retina in both the dry and wet types of AMD. They play a role not only in inflammation but also in stimulating retinal cell death and the development of new blood vessels, two important characteristics of AMD. Prof. Chowers has also shown in animal models for AMD and in cell culture that perturbation/modulation of macrophage, including decreasing their number and migration and changing their phenotype (behavior) could serve as a novel therapeutic strategy for AMD. To this end, Prof. Chowers and his research team are currently performing a large-scale screen using several relevant experimental systems to identify the ideal compound that may safely and effectively modulate macrophage involvement in AMD.

In search of the “holy grail” for the treatment of AMD and other harmful eye diseases, Prof. Chowers together with Prof. Eyal Banin have established the Center for Clinical Research in Ophthalmology, the only such center in Israel. This facility’s mission is to carry out translational research concerned with the application of laboratory or “bench” science to clinical trials. Dr. Chowers's objective is to understand the pathogenesis of AMD so that it can provide the first effective therapy for dry AMD and complement the existing therapy for the wet AMD, via targeting macrophage involvement in the disease. Thus, his ultimate goal is to save sight and reduce the socio-economic burden caused by this disease.