The renin-angiotensin system (RAS), that is known for its role in the regulation of blood pressure as well as in fluid and electrolyte homeostasis, comprises dozens of angiotensin peptides and peptidases and at least six receptors. Six central components constitute the two main axes of the RAS cascade. Angiotensin (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)-MasR) counterbalances the harmful effects of the angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R) Whereas systemic RAS is an important factor in blood pressure regulation, tissue-specific regulatory system, responsible for long term regional changes, that has been found in various organs. In other words, RAS is not only endocrine but also complicated autocrine system. The human eye has its own intraocular RAS that is present e.g. in the structures involved in aqueous humor dynamics. Local RAS may thus be a target in the development of new anti-glaucomatous drugs. In this review, we first describe the systemic RAS cascade and then the local ocular RAS especially in the anterior part of the eye.

The purpose of this study was to examine the protein profile differences between capillary and Schirmer strip tear fluid samples. Methods: Both capillary and Schirmer strip tear samples were collected from 31 healthy participants at the same visit, and the samples were analyzed with nanoflow liquid chromatography coupled with time-of-flight mass spectrometer (NanoLC-MSTOF), implementing a sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS). Sample type-specific and combined spectral libraries were used to evaluate the differences between the sample types in protein expression levels and biological functions. Results: In proportion, more extracellular proteins connected to immune response were quantified from the capillary samples while Schirmer strip samples contained more intracellular proteins. The sample types yielded similar counts of quantified proteins when a combined spectral library including both sample types was implemented. The differential expression analysis between the sample types identified proteins increased in the capillary samples (e.g., immunoglobulins) and Schirmer strip samples (e.g., heatshock proteins, annexins, and S100 proteins). Conclusions: Tear proteomics data originating from the same participants vary depending on whether the sample is collected with capillary or Schirmer strip, although there is also overlap between the two sample types when a combined spectral library is implemented in the SWATH-MS analysis. In discovery-based proteomics research of tear fluid, appropriate sampling method should be chosen carefully based on the research focus. Translational Relevance: Currently, there is no consensus on how the tear fluid sampling methods affect the resulting proteomics data, and hence, identification of the most suitable sampling methods for clinical researchers with varying research interests is important.

Background: The main purpose of the study was to establish whether essential components of the renin-angiotensin system (RAS) exist in the human aqueous humor.Methods: Forty-five patients ≥ 60 (74±7) years of age undergoing cataract surgery at Tampere University Hospital were randomly selected for the prospective study. The exclusion criterion was the use of oral antihypertensive medicine acting via renin-angiotensin system. Aqueous humor samples were taken at the beginning of normal cataract extraction. The samples were frozen and stored at -80 °C. The concentrations of intraocular endogenous RAS components Ang(1-7), ACE2, and ACE1 were measured using ELISA.Results: Concentration medians of Ang(1-7), ACE2, and ACE1 in the aqueous humor were: Ang(1-7) 4.08 ng/ml, ACE2 2.32 ng/ml and ACE1 0.35 ng/ml. The concentrations were significantly higher in glaucomatous than in non-glaucomatous eyes, ACE1 (p=0.014) and Ang(1-7) (p=0.026) vs non-glaucomatous eyes.Conclusions: Ang(1-7), ACE2 and ACE1 are found in the human aqueous humor. The observations are consistent with the conception that local tissue-RAS exists in the human eye and it might have a role in the control of intraocular pressure.

An active local intraocular renin-angiotensin system (RAS) has recently been shown to exist in the human eye, and evidence is now accumulating that antihypertensive drugs acting on RAS can also lower intraocular pressure. They seem also to work as neuroprotective agents against retinal ganglion cell loss in vivo; though no compounds are in ophthalmological use at present. Classically, the highly vasoconstrictive angiotensin II (Ang II) is the key peptide in the circulatory RAS. However, the final effect of RAS activation at tissue level is more complex, being based not only on the biological activity of Ang II but also on the activities of other products of angiotensinogen metabolism, often exerting opposite effects to Ang II action. Intraocular Pressure (IOP)The pressure inside the eye is maintained by a homoeostatic balance of formation and out-flow of intraocular fluid, aqueous humour (AH). AH formation rate of the healthy human eye is 2.5-2.8 ll ⁄ min, and the entire volume is replaced every 100 min. Under normal conditions, active secretion accounts for 80% to 90% of total AH formation. From the posterior chamber, AH flows around the lens and through the pupil into the anterior chamber, from which it leaves the eye mainly through pathways at the anterior chamber angle ( fig. 1). Normal IOP is 15.5 (€2.6) mmHg (mean € SD), and an IOP over 20.5 ( € 2.0) mmHg could be considered as upper limit of normal IOP [1].AH is secreted by the non-pigmented ciliary epithelial cells (NPEC) lining the ciliary processes mainly by active ionic transport across the epithelium against a concentration gradient ( fig. 2). Active secretion requires energy, which is normally provided by the hydrolysis of adenosine triphosphate by Na + ⁄ K + ATPase [2,3]. In addition to the active secretion, there are two essential passive physiological processes in the formation of AH: diffusion from the blood compartment and ultrafiltration. AH leaves the eye principally (90%) through the trabecular meshwork (TM) in the chamber. A smaller proportion (10%) of AH makes its way directly into the ciliary body and is drained by way of the ciliary muscle, the suprachoroidal space and the sclera. This is called uveoscleral or unconventional out-flow [2]. Regulation of IOPThe eye is a specific organ in many respects. The globe has no lymphatic tissue, its vascular supply is unique with two blood-ocular barriers [4], it has its own autoregulation in blood circulation, and there is a tissue with dense vasculature (choroidea) as well as tissues without any vessels such as the vitreous body and the lens. It is known that ocular blood flow depends on many factors such as perfusion pressure (i.e. mean arterial blood pressure -IOP) and the resistance to flow as determined by the vascular calibre in the arterioles and capillaries. The latter is influenced by factors that affect local tissue blood flow, e.g. endothelial vasodilators (nitric oxide, prostacyclin) or vasoconstrictors (angiotensins, endothelins). The autoregulation system keeps the local ti...