Abstract
Exfoliation glaucoma (XFG) is the most recognizable form of secondary open-angle glaucoma associated with a high risk of blindness. This disease is characterized by white flaky granular deposits in the anterior chamber that leads to the elevation of intraocular pressure (IOP) and subsequent glaucomatous optic nerve damage. Conventionally, XFG is known to respond poorly to medical therapy, and surgical intervention is the only management option in most cases. Various genetic and nongenetic factors are known to be linked to the development of XFG. Despite decades of research on the genetic factors in exfoliation syndrome (XFS) by study groups and global consortia involving different ethnic populations, the pathogenesis of XFS and the mechanism of onset of glaucoma still remains an unsolved mystery. The key lies in understanding how the function of a gene (or set of genes) is altered by environmental triggers, along with other molecular events that underlie the key disease attributes, namely, oxidative stress and the disruption of the blood–aqueous barrier (BAB). It remains a challenge to evolve a theory encompassing all factions of molecular events occurring independently or parallelly that determine the disease manifestation (phenotype) or the stage of the disease in the eye (or in any tissue) in exfoliation. Our enhanced understanding of the underlying molecular pathophysiology of XFG, beyond the known genes or polymorphisms involved in the disease, will lead to improved diagnosis and management and the ability to recognize how the environment influences these key events that lead to the disease phenotype or disease progression. This review summarizes the recent observations and discoveries of four key factors that may hold the answers to the non-lysyl oxidase-like 1 (LOXL1) mechanisms behind XFG pathogenesis, namely, the epigenetic factor miRNA, disordered autophagy along with the potential involvement of mitochondrial mutations, and a compromised aqueous–blood barrier.
Highlights
Exfoliation glaucoma (XFG) is a severe and progressive type of sight-threatening [1,2]disease, a systemic fibrillopathy, and is one of the most commonly recognizable, clinically unique form of open-angle glaucoma [2–4]
Genome-wide association study performed in 2007 by Thorleifsson and coworkers first showed that three single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with a risk of
We performed a literature search of the PubMed database, identifying all articles associated with XFG and XFS using the following MeSH terms: exfoliation glaucoma, exfoliation syndrome, autophagy, miRNAs, mitochondria, and blood–aqueous barrier
Summary
Exfoliation glaucoma (XFG) is a severe and progressive type of sight-threatening [1,2]. Disease, a systemic fibrillopathy, and is one of the most commonly recognizable, clinically unique form of open-angle glaucoma [2–4]. Patients with XFG present with more severe optic nerve damage and visual loss at presentation, are refractory to medical treatment, and are associated with a faster rate of progression compared to other forms of primary glaucoma [3,4]. Other genes implicated in XFG include calcium voltage-gated channel subunit alpha. AOther genes implicated in XFG includeprotein calcium(POMP), voltage-gated channel subunit. 3 (RBMS3), and semaphorin genetic several etiologygroups is complicated by the frequent occurrence of LOXL1 SNPs among healthy. Though have identified several key genes responsible for the disease, the genetic is complicated by the frequent occurrence of LOXL1. (XFS)to toexfoliation exfoliationglaucoma glaucoma(XFG).TGF(XFG).TGFβ1—transforming β1—transforminggrowth growthfactor-beta; factor-beta1;BAB—blood–aqueous.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
