JUL 22, 2015

Inhibiting Mast Cell Degranulation: A New Therapy For Macular Degeneration

WRITTEN BY: Kara Marker
The American Journal of Pathology recently published a study that yields promising results in the search for better treatment options for people suffering from chronic eye problems like macular degeneration. Essentially, problems result from these disorders because fluid accumulates in and around the retina when mast cells release substances during degranulation. Scientists in the recently published study found a compound that could inhibit the release of substances, making it a potential new therapy for chronic eye problems.


Mast cells are immature leukocytes (white blood cells) circulating in the blood before they move on to tissues to differentiate into more specific cells. "Within seconds of stimulation, mast cells can undergo degranulation," releasing factors like histamine (PLoS Pathogens). Histamine is a compound that, in response to an infection of foreign particles, opens up pores in small blood vessels to allow leukocytes and proteins access to fight the foreign invaders. Histamine and other products of degranulation can lead to a buildup of fluid in the retina.

The theory in this new study is that "repeated exposure to stimuli" induces degranulation of mast cells, and over time, the large amount of degranulation products emitted from mast cells contributes to chronic eye problems. To test this theory, scientists compared three experimental groups of test rats' eyes: 1) rats with a right eye injection of a degranulation-activating compound, 2) the non-injected left eye of the same rat, and 3) rat eyes injected with only saline solution.

The experiment resulted in visible mast cell degranulation after 15 minutes post-injection with the intended compound, while "no clinical abnormalities were seen in the untreated left eye." They used optical coherence tomography (OCT), a new technique that uses light to provide images of tissue structure, similarly to how ultrasound uses sound to produce pictures (Neoplasia Press). The OCT results showed "large and multiple retinal serous detachments" in the rat eyes treated with the mast cell degranulation-activating compound.

In the next part of the experiment, the scientists discovered that another compound, disodium cromoglycate, lowered the rate of serous retinal detachment from 80% to 16% when it was administered before the degranulation-activating compound. Disodium cromoglycate was found in 1969 to "inhibit discharge of the mediators of mast cells" (Nature). At the time it was used to experimentally reduce the allergic response of asthmatics, but in the current study it is also effective at indirectly treating eye problems associated with retinal detachment.

In the future, scientists hope to use disodium cromoglycate as part of the treatment for macular degeneration and other chronic eye problems caused by retinal detachment. Check out the video below to understand better the characteristics of macular degeneration:



Source: Elsevier