In Graves' disease, which substance accumulation leads to inflammation and edema in the orbit?

In Graves' disease, the accumulation of glycosaminoglycans (GAGs) in the orbit is responsible for the inflammation and edema associated with thyroid eye disease, also known as Graves' ophthalmopathy. GAGs, such as hyaluronic acid, attract water, leading to an increase in extracellular matrix volume and causing the swelling and protrusion of the eyes (exophthalmos) seen in this condition.

The pathophysiology involves an autoimmune reaction where autoantibodies stimulate the thyroid gland, resulting in hyperthyroidism. Simultaneously, these antibodies can also target orbital fibroblasts, leading to increased production of GAGs. This accumulation results in tissue expansion, inflammation, and edema in the ocular region, manifesting clinically as bulging eyes and potential compression of the optic nerve.

Other options, while related to the broader context of Graves' disease, do not specifically account for the ocular manifestations. Thyroid hormones primarily affect metabolic processes but do not directly cause the orbital edema. Autoantibodies contribute to the disease mechanism but are not the substances that accumulate in the orbit itself. Cytokines play a role in inflammation but are not the primary mediators of the edema associated with Graves' ophthalmopathy.