Glaucoma in Iran and contributions of studies in Iran to the understanding of the etiology of glaucoma

Epidemiologic and genetic/molecular research on glaucoma in Iran started within the past decade. A population-based study on the epidemiology of glaucoma in Yazd, a city in central Iran, revealed that 4.4% of studied individuals were affected with glaucoma: 1.6% with high tension primary open angle glaucoma (POAG), 1.6% with normal tension POAG, and 0.4% each with primary angle closure glaucoma (PACG) and pseudoexfoliation glaucoma (PEXG), and other types of secondary glaucoma. Two notable observations were the relatively high frequency of normal tension glaucoma cases (1.6%) and the large fraction of glaucoma affected individuals (nearly 90%) who were unaware of their condition. The first and most subsequent genetic studies on glaucoma in Iran were focused on primary congenital glaucoma (PCG) showing that cytochrome P450 1B1 (CYP1B1) is the cause of PCG in the majority of Iranian patients, many different CYP1B1 mutations are present among Iranian patients but only four mutations constitute the vast majority, and the origins of most mutations in the Iranians are identical by descent (IBD) with the same mutations in other populations. Furthermore, most of the PCG patients are from the northern and northwestern provinces of Iran. A statistically significant male predominance of PCG was observed only among patients without CYP1B1 mutations. Clinical investigations on family members of PCG patients revealed that CYP1B1 mutations exhibit variable expressivity, but almost complete penetrance. A great number of individuals harboring CYP1B1 mutations become affected with juvenile onset POAG. Screening of JOAG patients showed that an approximately equal fraction of the patients harbor CYP1B1 and (myocilin) MYOC mutations; MYOC is a well-known adult onset glaucoma causing gene. Presence of CYP1B1 mutations in JOAG patients suggests that in some cases, the two conditions may share a common etiology. Further genetic analysis of Iranian PCG patients led to identification of Latent-transforming growth factor beta-binding protein 2 (LTBP2) as a causative gene for both PCG and several diseases which are often accompanied by glaucomatous presentations, such as Weill-Marchesani syndrome 3 (WMS3). The findings on LTBP2 have contributed to recognize the importance of the extracellular matrix in pathways leading to glaucoma.