Caveolin-1 in vascular health and glaucoma: A critical vascular regulator and potential therapeutic target

Abstract

Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found in most cell types. Cav-1 has been found to contribute significantly to ocular function, with mutations of Cav-1 being associated with a genetic risk of glaucoma development. Raised intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. Cav-1 may be involved in both IOP-dependent and independent mechanisms involving vascular dysregulation. Systemic vascular diseases including hypertension, diabetes and hyperlipidaemia, have been shown to be associated with glaucoma development. Cav-1 is closely interlinked with endothelial nitric oxide synthase pathways that mediate vascular function and prevent cardiovascular diseases. Endothelial nitric oxide synthase and endothelin-1 are key vasoactive molecules expressed in retinal blood vessels that function to autoregulate ocular blood flow (OBF). Disruptions in the homeostasis of OBF have led to a growing concept of impaired neurovascular coupling in glaucoma. The imbalance between perfusion and neuronal stimulation arising from Cav-1 depletion may result in relative ischemia of the optic nerve head and glaucomatous injury. OBF is also governed by circadian variation in IOP and systemic blood pressure (BP). Cav-1 has been shown to influence central BP variability and other circadian rhythms such as the diurnal phagolysosomal digestion of photoreceptor fragments and toxic substrates to maintain ocular health. Overall, the vast implications of Cav-1 on various ocular mechanisms leading to glaucoma suggest a potential for new therapeutics to enhance Cav-1 expression, which has seen success in other neurodegenerative diseases.

Molecular Mechanisms of Glaucoma Pathogenesis with Implications to Caveolin Adaptor Protein and Caveolin-Shp2 Axis

“…Vascular tone abnormality is another risk factor for POAG with links to Cav-1. Interestingly, the CAV-1 gene as a vascular tone regulator [140] showed a higher level of association with patients with glaucomatous paracentral visual field loss who were more likely to have systemic vascular dysfunction [38,141]. This is consistent with a retinal vascular phenotype and systemic vascular alterations observed in Cav-1 -/mice [142].…”

Is Primary Open-Angle Glaucoma a Vascular Disease? Assessment of the Relationship between Retinal Arteriolar Morphology and Glaucoma Severity Using Adaptive Optics

“…Further investigations of vascular changes in glaucoma would be helpful for better understanding its multifactorial pathogenesis, analysing the causes and effects of vascular and neurodegenerative changes in glaucoma, and the future invention of therapeutic targets, such as endothelin or Caveolin receptors, which can dilate retinal vessels and increase blood flow [2,55]. AO technology, due to its high resolution and image quality, allows the assessment of glaucomatous changes at the cellular level not only in the vessels but also in other structures such as nerve fibres [56][57][58], the lamina cribrosa [59], photoreceptors [60], trabeculae [61], and retinal ganglion cells [62,63].…”

Is Primary Open-Angle Glaucoma a Vascular Disease? – Assessment of the Relationship of Retinal Arteriolar Morphology and Glaucoma Severity Using Adaptive Optics

“…All these observations suggest that significant vascular alterations are primary in POAG. These investigations may enable the identification of potential targets for future glaucoma treatments, such as endothelin or Caveolin receptors, which can dilate retinal vessels and increase blood flow [2,56]. While numerous studies substantiate the existence of a vascular mechanism leading to neurodegenerative glaucoma damage, it is essential not to forget that glaucoma itself can initiate retinal vascular abnormalities as secondary manifestations of the disease [7,9,57,58].…”