Introduction:
Optic neuropathy, in which progressive degeneration of retinal ganglion cells (RGCs) occurs, is known as glaucoma. Affects more than 70 million people worldwide. Intraocular pressure (IOP) is a risk factor for glaucoma. Renin-angiotensin-aldosterone system (RAAS) helps in the regulation of blood pressure. Activation of RAAS causes cell proliferation, inflammation, oxidative stress, and stimulation of fibrosis by angiotensin II (Ang II) and aldosterone. Aldosterone effects can be seen only after it gets bound to MR. These effects influence heart, kidney, electrolyte balance, and vascular pathology. RAAS is present in the retina. Studies have shown that aldosterone plays a role in eye diseases.
What Is Aldosterone?
A mineralocorticoid hormone is secreted in the adrenal cortex and regulates water and salt in the body. Its main function is to act on the distal tubule and collect ducts of nephrons in the kidney in the reabsorption of sodium, water, and potassium. Ang II helps release aldosterone from the adrenal cortex. A study observed that, as in the heart, brain, and vasculature, the eye has an aldosterone-MR system. This system plays a role in the development of retinal vasculopathy.
How Is Aldosterone Related to the Eyes?
The eye contains the aldosterone-MR system. Conditions like premature damage of the retina, diabetic retinopathy due to increased blood sugar levels, and age-related degeneration of the eyes are angiogenic. These are responsible for vision loss. These pathological processes involve microaneurysms, hemorrhages, exudates from vessels, retinal detachment due to fibrosis, and neovascular glaucoma leading to increased IOP. Ischemic changes, inflammation, and growth factor-induced angiogenesis are the basic features of retinopathy, although the correct mechanism to know is very tricky about retinopathy.
What Is the Mechanism Involved?
The vascular endothelial growth factor (VEGF) is related to vascular permeability and angiogenesis. VEGF sends a signal using VEGF receptor 1 (FMS-like tyrosine kinase-1) and VEGF receptor 2 (fetal liver kinase). VGEF uses protein kinase C, mitogen-activated protein kinases, and reactive oxygen species (ROS) for signals. VEGF activity is increased by glucose, advanced glycation end products, growth factor-β, and insulin growth factor -1, which are, in turn, regulated by the renin-angiotensin-aldosterone system.
The eye possesses RAAS. Hence targeting RAAS is more effective in treating retinal vasculopathy as Ang II and aldosterone are proinflammatory, fibrogenic, and angiogenic. As the RAAS system is present in the eye, all components are seen in the eye. Renin, angiotensin-converting enzyme, angiotensinogen, Ang II, and Ang II receptors are present in humans in the vasculature, neurons, and glia. Components of RAAS are increased in diabetic patients-leading to the severity of retinopathy.
What Is Primary Aldosteronism?
Primary aldosteronism is the increased production of aldosterone by adrenal glands. Hypertension, cardiovascular damage, sodium retention, suppression of plasma renin, and hypokalemia are the causes of PA.
The frequency of occurrence of PA is 5 % in hypertension and 20 % in hypertension with various complications. Patients of PA are at risk of hypertensive retinopathy, retinal vascular occlusion, and non-arteritic anterior ischemic optic neuropathy. Studies have shown an association between PA and central serous chorioretinopathy. A study showed that PA might be responsible for glaucomatous optic neuropathy.
What Are Other Effects of Aldosterone on the Eye?
The effects of aldosterone on the eyes are as follows:
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Retinal Vein Occlusion (RVO): RVO is the second most common cause of vision loss. A study has shown that RVO is specifically associated with a high aldosterone level. Ischemic RVO is seen in PA patients.
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Central Serous Chorioretinopathy (CSCR): CSCR is a choroidal vascular disease affecting men in middle age. It is shown and hypothesized that inappropriate activation of MR results in CSCR.
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Choroidal Neovascularization (CNV): CNV is associated with aldosterone. CNV is a vascular disease where choroidal neovessels invade Bruch’s membrane, the sub-retinal pigment epithelial space, and subretinal space, resulting in loss of central vision.
What Is the Mechanism of Aldosterone Responsible for Retinal Vascular Disease?
The target cells involved are vasculature itself. Effects of aldosterone on vascular cells, endothelial cells (EC), vascular smooth muscle cells, and pericytes were studied to know the mechanism of aldosterone in hypertension and cardiovascular diseases. Increased reactive oxygen species (ROS) lead to vascular inflammation, increased thrombosis, and cardiovascular diseases.
Aldosterone increases the transcription and plasma membrane translocation of various components of nicotinamide adenine diphosphate (NADPH) oxidase complex, including Nox2, Nox4, p22phoxn, and p47phox in endothelium which leads to more production of ROS.
A study showed the presence of RAAS in retinal microvasculature cells and found aldosterone effects on both cultured ECs and oxygen-induced retinopathy (OIR) model.
Another mechanism is through inflammatory mediators where aldosterone mediated endothelial expression of ICAM1 and MCP1 involving macrophages into retinal vascular diseases.
Aldosterone impacts muller glial cells, which are responsible for vascular function, water homeostasis, and extracellular milieu.
What Are the Treatments for the Effects of Aldosterone on the Eye?
Effects of aldosterone on the eye can be treated by using the following methods:
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RAAS is interrupted by angiotensin-converting enzyme inhibitors or Ang II type 1 (AT1) receptor blockers.
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Prorenin, a peptide, binds to the renin receptor as a decoy peptide and inhibits the nonproteolytic activation of prorenin.
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Candesartan significantly reduced retinopathy in type 1 diabetes, beneficial effects were observed on retinopathy progression in type 2 diabetes and supported RAAS’s role in the pathophysiology of retinopathy.
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MR antagonists with spironolactone improve retinal angiogenesis by attenuating leukostasis and decreasing proinflammatory responses.
Conclusion:
Aldosterone is a hormone secreted in the body. Understanding hormones and their actions are very challenging. The actions of hormones vary in different individuals. Its role in the eye is understood. Knowing about the effects of aldosterone on the eyes helps prevent the harmful complications of retinopathy that result in irreparable vision loss.
