Potential benefit of angiotensin converting enzyme inhibitors for hindering progression of graves’ ophthalmopathy

Abstract

The eye disease often associated with Graves’ thyroid disease is referred to as Graves’ ophthalmopathy, it is primarily a disease of the orbit and has also been called Graves’ orbitopathy. The volume of both the extraocular muscles and retroorbital connective and adipose tissue is increased, due to inflammation and the accumulation of hydrophilic glycosaminoglycans (GAG), principally hyaluronic acid, in these tissues [1]. The accumulation of GAG causes a change in osmotic pressure, which in turn leads to a fluid accumulation and an increase in pressure within the orbit and displace the eyeball forward. TGF-b, an important cytokine involved in cell growth and differentiation is involved in tissue repair and fibrosis by regulating extracellular matrix production [2]. This cytokine can up-regulate GAG synthesis in cultured human orbital fibroblasts [3]. TGF-b induced hyaluronic acid synthesis is mediated by PKCII and Ca in normal orbital fibroblasts and orbital fibroblasts from patients with Graves’ ophthalmopathy [2]. It has been reported that serum angiotensin converting enzyme (ACE) level increases during hyperthyroidism, and there is a strong correlation between ACE activity and thyroid hormone concentrations [4]. On the other hand angiotensin II potently induces synthesis of transforming growth factor TGF-b [5]. Components of RAS system was localized in the human ocular tissues [6,7]. Thus up-regulation of this system in hyperthyroidism and increase in serum and tissue angiotensin II level may activate synthesis of TGF-b and consequently hyaluronic acid accumulation in the orbital tissue. Accordingly angiotensin converting enzyme inhibitors may hinder the progression of thyroid ophthalmopathy by preventing activation of TGF-b and decreasing deposition of hyaluronic acid as the major hydrophilic GAG leading to fluid accumulation and clinical manifestations of thyroid ophthalmopathy.