Exfoliation Syndrome and Exfoliative Glaucoma 203ROLE OF GENETIC ALTERATIONS, ENVIRONMENTAL
FACTORS AND OXIDATIVE STRESS IN THE
DEVELOPMENT OF EXFOLIATION SYNDROME
AND EXFOLIATIVE GLAUCOMA
XFS is a genetically determined condition. It has recently been shown that
2 common single nucleotide polymorphisms (SNPs) of the lysyl oxidase-like
protein 1 (LOXL1) gene are responsible for almost 100% of the population-
related risk of XFS [26,27]. In most white populations the risk alleles are
G153D and R141L [26,27]. The LOXL1 protein is responsible for elastin
production and turnover in the whole body, thus its disturbed translation and
dysfunction explain several characteristics of intraocular and systemic
alterations in XFS [16,28]. It is important to note, however, that there are
different risk alleles in various populations and these are also common in
healthy individuals in whom XFS never develops [26]. Thus, currently
unknown environmental factors are also believed to take part in the
development of XFS. Very recently a novel association between XFS and
calcium signaling has been established: one SNP of the calcium voltage-gated
channel subunit alpha1A gene (CACNA 1A) confers 1.16 times increased risk
for XFS [29]. The exact mechanism of LOXL1 and CACNA1A
polymorphisms causing XFS remains to be determined.
It is important to recognize that conversion from XFS to XFG is not
genetically determined, thus any genetic screening for XFG is impossible. The
conversion from XFS to XFG is considered a result of environmental factors
[26,30-32]. The common mechanism of all environmental factors seems to be
increased oxidative stress in the anterior chamber [28,30,33]. According to the
current hypothesis, increased sunshine exposure provokes production of
oxidative stress markers (e.g., 8-ioprostaglandin F2α, endothelin 1) and
depletion of antioxidant protection molecules (e.g., ascorbic acid) in the
anterior chamber [33]. The oxidative stress, which is greater in XFG than in
XFS, is supposed to cause nuclear cataract, dysfunction of the trabecular
meshwork and zonular damage. The trabecular meshwork dysfunction is
considered responsible for the IOP elevation and the large IOP fluctuation
typical in XFG, and the zonular damage for phacodonesis, lens dislocation, or
secondary angle closure glaucoma (when the luxated lens causes pupillary
block or directly blocks the anterior chamber angle) [4]. Recently, based on
population-based retrospective studies, it has been suggested that the amount
of time spent outdoor in bright sunshine without sunglasses in young age (a