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Research: Role of HDL3 cholesterol in primary open-angle glaucoma

Glaucoma is the age-related leading cause of irreversible blindness worldwide, with the number of cases expected to increase with aging populations to reach 111.8 million by 2040. Glaucoma is a multifactorial condition characterized by a progressive degeneration of optic nerve and retinal ganglion cells, with distinctive visual field loss. Primary open-angle glaucoma (POAG) is the most prevalent form of glaucoma. Several risk factors of POAG are well known such as age, elevated intraocular pressure (IOP) or ethnicity, however, the presence and role of modifiable risk factors needs to be further elucidated. For example, the role of lipids is not well understood and the findings conflicting.

In a recent study by Dr Simon Nusinovici and Prof Cheng Ching-Yu's that was published in Ophthalmology, they have identified HDL3 cholesterol as being causally and specifically associated with POAG. This finding suggest that dysregulation of cholesterol transport may play a role in the pathogenesis of POAG.

They have first identified HDL3 cholesterol as being associated with POAG among 130 blood lipid-related metabolites using statistical modelling (Figure 1). Individuals with POAG had lower levels of HDL3 cholesterol. Then, they have used genetic information to demonstrate the causality of this association by using a Mendelian Randomization approach. Furthermore, interestingly, none of the routine lipids, such as blood total high-density lipoprotein (HDL) or low-density lipoprotein (LDL), were associated with POAG, which indicated the specificity of HDL3 cholesterol in POAG pathophysiology. This finding is the first step towards the understanding of the roles of the lipids in POAG pathophysiology and could be useful in the identification of new drug target.


Figure 1: Graphical network representing the associations among POAG, lipid-related metabolites, and other possible POAG risk factors.


For more information, watch this video as Dr Simon Nusinovici discusses on his research work:
Internet access required



Contributed by:


 Dr Simon Nusinovici
 Assistant Professor, SingHealth Duke-NUS (EYE ACP)
 Research Fellow, Ocular Epidemiology Research Group
 Singapore Eye Research Institute

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