Vascular and autonomic dysregulation in primary open-angle glaucoma

Abstract

Purpose of the review To discuss whether vascular dysfunction and autonomic dysfunction are related to primary open-angle glaucoma stratified by the intraocular pressure (IOP) level (the high tension glaucoma and normal tension glaucoma subtypes). Recent findings Patients with POAG across the spectrum of IOP exhibit a variety of ocular and non-ocular vascular abnormalities. Interestingly common genetic variation in NOS3 and the CAV1/CAV2 genomic regions, which code for proteins involved in setting vascular tone, are associated with POAG. These markers seem to stratify with POAG subtypes by sex or pattern of initial visual field loss. Overall it is clear that there is also cardiovascular autonomic dysfunction in HTG and NTG but it is unclear if this dysfunction is more common in NTG compared to HTG. Summary Overall POAG is likely a heterogeneous disease but stratifying cases by IOP level associated with initial optic nerve damage may be less useful than using other endophenotype approaches. Embracing the evidence suggesting systemic endothelial and autonomic dysfunction are operative in POAG will help move beyond an IOP-centric view of the disease and facilitate “tearing down the wall” that divides treating physicians and a better understanding of POAG pathogenesis.

Caveolins and caveolae in ocular physiology and pathophysiology

“…Thus, the retinal vasculature is likely to be intrinsically more reliant on caveolae-regulated myogenic control and thus more sensitive to caveolae deficiency than systemic vasculature. This hypothesis is consistent with our current data and merits more attention given the association of CAV1 polymorphisms with primary open angle glaucoma (POAG) and the potential of vascular tone dysregulation to play a role in POAG (Kang et al, 2014; Pasquale, 2016). …”

“…Vascular tone is an additional contributor to POAG risk and impaired autoregulation and blood flow has been reported (reviewed in (Flammer et al, 2002; Hayreh, 2001; Pasquale, 2016). Genes (including CAV1 ) involved in local control of vascular tone are more strongly associated with POAG with early paracentral visual field loss (Kang et al, 2014; Loomis et al, 2014).…”

Glaucoma as a Metabolic Optic Neuropathy: Making the Case for Nicotinamide Treatment in Glaucoma

“…Vasculature dysfunction is implicated in glaucoma 91, 92 . NAM can improve endothelial function and stabilize blood flow by preventing transient flow interruptions 93 .…”

Neuroprotection in glaucoma: recent advances and clinical translation

“…108,109 This could be explained by the inhibition of oxidative inactivation of -SH containing enzymes such as GAPDH and pyruvate kinase, and the continued regeneration of NAD+ (produced during the reduction of pyruvate to lactate by LDH) with consequent stimulation of the oxidation of glyceraldehyde-3-phosphate to 1,3 diphosphoglycerate by GAPDH dependent on NAD+ availability. 135,137,138 Its physiological efficacy in glaucoma is supported by its favourable effects on calcium channel and calcium signalling (important in axon degeneration), [139][140][141] its vasoactive properties (with vascular dysfunction implicated in glaucoma) 142,143 and its ability to improve endothelial function and stabilizing blood flow by reversing endothelinmediated vasoconstriction (with endothelin receptor blockers shown to protect against glaucoma). 135,136 NAM is unique among NAD precursors because it is a physiological inhibitor of the major NAD catabolic enzymes, namely CD38, PARPs (Poly (ADP-ribose) polymerase) and SIRTs (sirtuin).…”