Common Molecular Challenges in Glaucoma

95 The clinical entity collectively known as glaucoma is a very specific optic neuropathy that affects individuals with various degrees of ocular complications and even with greater degrees of genetic heterogeneity.[1,2] Although the very first genetic contribution to this group of eye disorders was described over 50 years ago,[3] it took another 30 years before the first molecular studies of this condition were undertaken.[4,5] The significant challenge in understanding the basic underlying genes, proteins, biochemical and molecular pathways that are involved in this group of disorders is due to many difficulties in accurate clinical diagnosis, classification, primary vs. secondary disease, as well as various degrees of both clinical and genetic heterogeneity.[6,7] Furthermore, lack of suitable large families, extreme ages of onset, racial ethnicity and many other limiting factors compound our ability to find the majority of defective genes and proteins for this ocular condition. It is against this background that finding or even relating certain mutations in one or more genes and their possible contributions to a specific form of glaucoma would be a significant addition to our understanding of the molecular basis of this condition. One such study is the current paper by Safari et al[8] in which they studied the possible role of the LTBP2 gene in the etiology of primary angle closure glaucoma (PACG) as well as a single case with both PACG and pseudoexfoliation glaucoma (PXFG). Although the LTBP2 gene was originally reported to be the cause of primary congenital glaucoma (PCG) in certain Pakistani[9] and Iranian[10] families, subsequent studies by other investigators failed to confirm this observation in a group of American[11,12] Turkish,[12] English,[12] Indian[13] and Saudi Arabian[14] PCG subjects. It is likely that the congenital glaucoma nature of patients reported in the earlier studies[9,10] were in fact of a secondary nature, as those patients had a series of other ocular and non‐ocular complications. Moreover, many other LTBP2 mutations have now been reported in megalocornea,[15] spherophakia,[15] microspherophakia,[15,16] ectopia lentis[17] and Weill‐Marchesani syndrome.[18] Interestingly, often these disorders are reported with secondary forms of glaucoma. Also, it has recently been reported that other Common Molecular Challenges in Glaucoma