The chemical composition of the human aqueous humour in normal and pathological conditions

doi:10.1016/S0014-4835(65)80030-6

Experimental Eye Research

Volume 4, Issue 3, September 1965, Pages 179-186

https://doi.org/10.1016/S0014-4835(65)80030-6 Get rights and content

By means of micro-techniques, a simultaneous analysis was made of 5 components of the human anterior aqueous humour under normal and pathological conditions (44 subjects). The mean values found, expressed in mmoles/kg H₂O, were: bicarbonates 20·15, lactic acid 4·50, ascorbic acid 1·16, chlorides 131; glucose 2·77. For the plasma, these values were: bicarbonates 27·52; lactic acid 1·93, ascorbic acid 0·046, chlorides 107, glucose 5·91. It was found that the concentrations in the aqueous humour were not correlated with various pathological conditions of the eye, and in particular with the state of transparency of the lens.

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Antioxidant enzymes such as superoxide dismutase, glutathione peroxidase,75 and catalase have also been identified in aqueous humor. In contrast to nocturnal animals, the corneal epithelium,76,77 lens,78 vitreous,9 and aqueous humor79,80 of diurnal animals contain extremely high levels of AsA compared to that in plasma.81 Shui and colleagues8 noted that metabolism of molecular oxygen in the vitreous gel occurs in an AsA-dependent manner, without an exogenous catalyst and independent of light, revealing the significance of AsA as a primary regulator of intraocular molecular oxygen.
The purpose of this study was to investigate correlations of partial pressure of oxygen (pO₂) in the ocular anterior segment of human eyes and aqueous humor antioxidant levels of ascorbate (AsA) and total reactive antioxidant potential (TRAP) with glaucoma and vitreous status.
This prospective, cross-sectional study stratified patients (n = 288 eyes) by lens and vitreous status and the presence of primary open-angle glaucoma for statistical analyses. Intraocular pO₂ concentrations were measured using a fiberoptic probe in patients at the beginning of planned glaucoma and/or cataract surgery. Aqueous humor specimens were obtained for antioxidant analysis of AsA and TRAP.
Following prior pars plana vitrectomy, pO₂ levels were significantly higher than in the reference group of cataract surgery in the anterior chamber angle (16.2 ± 5.0 vs. 13.0 ± 3.9 mm Hg; P = .0171) and in the posterior chamber (7.6 ± 3.1 vs. 3.9 ± 2.7 mm Hg; P < .0001). AsA and TRAP levels were significantly lower (1.1 ± 0.4 vs. 1.4 ± 0.5 mM, respectively; 403.3 ±116.5 vs. 479.0 ± 146.7 Trolox units, respectively; P = .004 and P = .024, respectively) in patients after vitrectomy. In patients with an intact vitreous, neither pO₂ nor antioxidant status correlated with lens status or glaucoma.
Increased pO₂ and antioxidant depletion following vitrectomy suggests an alteration of the intraocular oxidant-antioxidant balance. Our study links physiologic factors such as increased pO₂ in the anterior chamber angle and the posterior chamber to decreased antioxidant levels in aqueous humor following vitrectomy. Oxidative stress/damage to the trabecular meshwork in such post-vitrectomy cases may contribute to intraocular pressure elevation and increased risk of glaucoma. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Pranoprofen quantification in ex vivo corneal and scleral permeation samples: Analytical validation
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Artificial aqueous humor. Based on the physiologic composition of aqueous humor and its properties [21–23], an artificial aqueous humor solution was prepared to immerse the eye samples during its transport to the laboratory. Its composition is detailed in Table 1.
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In vitro to in vivo transposition is a delicate exercise, particularly in the ophthalmic context. Indeed, all individual variability such as the eye anti-UV filter’s capacity, the aqueous humor’s composition (especially metallic ions) and the oxygen level in the eye, polyacrylate copolymers can age in different proportions between patients [87–89]. The co-morbidities of patients and the health practices both increase the variety of aging scenarios [90].
Photooxidation and hydrolysis are the two primary aging factors of intraocular lenses. Opacifications, dislocations, glistening and yellowing of the implanted acrylic lenses, which are due to chain scissions and depolymerization, are the consequences of aging from the clinical perspective. The purpose of this study was to examine the consequence of the aging of intraocular lenses on chemical and surface properties. Acrylic lenses made of poly acrylic-co-polystyrene polymer were artificially aged by photooxidation and hydrolysis from 2 to 20 years. Degradation products were observed by Reverse-phase High-Performance Liquid Chromatography RP-HPLC and thermogravimetric analysis (TGA). The surface, which was analyzed by atomic force microscopy (AFM) and fibronectin adhesion kinetics, was chosen as an indicator of intraocular biocompatibility. Low-molecular-weight degradation products (LMWP) result from chain scission under both hydrolysis and photooxidation. The osmotic effects of water enable degradation products to migrate through the polymer. A portion of the degradation products exudate in the surrounding center, whereas a portion link with lateral chains of the polymer. At the same time, the surface roughness evolves to externalize the most hydrophilic chains. As a result, the fibronectin adhesion level decrease with time, which indicates the existence of a biocompatible kinetic for implanted intraocular lenses.
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In addition, the presence of tight junctions in both tissues constitutes an obstacle for permeation of drugs, especially through the cornea (Yoshida et al., 2009). The aqueous humor is also part of the anterior segment and it is mostly composed of water and electrolytes, low molecular weight compounds and proteins (de Berardinis et al., 1965; Tripathi et al., 1989). The posterior segment is protected by the sclera, which represents the continuation of the cornea, and it is formed by the vitreous humor, retina, choroid and optical nerve.
This review is a comprehensive analysis of the progress made so far on the delivery of polynucleotide-based therapeutics to the eye, using synthetic nanocarriers. Attention has been addressed to the capacity of different nanocarriers for the specific delivery of polynucleotides to both, the anterior and posterior segments of the eye, with emphasis on their ability to (i) improve the transport of polynucleotides across the different eye barriers; (ii) promote their intracellular penetration into the target cells; (iii) protect them against degradation and, (iv) deliver them in a long-term fashion way. Overall, the conclusion is that despite the advantages that nanotechnology may offer to the area of ocular polynucleotide-based therapies (especially AS-ODN and siRNA delivery), the knowledge disclosed so far is still limited. This fact underlines the necessity of more fundamental and product-oriented research for making the way of the said nanotherapies towards clinical translation.
The exit strategy: Pharmacological modulation of extracellular matrix production and deposition for better aqueous humor drainage
2016, European Journal of Pharmacology
Citation Excerpt :
Then it flows from the posterior chamber, through the pupil and fills the anterior chamber (Bill, 1973; Green and Pederson, 1973). Aqueous humor is a colorless colloidal fluid composed of ions (sodium, potassium, calcium, magnesium, chloride, bicarbonate), low molecular weight substances (sugars, ascorbate, lactate, pyruvate, urea, hydrogen peroxide, cyclic nucleotides, amino acids), macromolecules (proteins, lipids), and biologically active substances (hormones, catecholamines, eicosanoids) (Consul et al., 1969; De Berardinis et al., 1965; Krause and Raunio, 1969a, 1969b). The major functions of aqueous humor are to (1) keep the cornea and the lens transparent (2) supply nutrients and oxygen to the anterior segment and (3) remove waste products from the anterior segment (Conrad and Funderburgh, 1992; Fautsch and Johnson, 2006).
Primary open angle glaucoma (POAG) is an optic neuropathy and an irreversible blinding disease. The etiology of glaucoma is not known but numerous risk factors are associated with this disease including aging, elevated intraocular pressure (IOP), race, myopia, family history and use of steroids. In POAG, the resistance to the aqueous humor drainage is increased leading to elevated IOP. Lowering the resistance and ultimately the IOP has been the only way to slow disease progression and prevent vision loss. The primary drainage pathway comprising of the trabecular meshwork (TM) is made up of relatively large porous beams surrounded by extracellular matrix (ECM). Its juxtacanalicular tissue (JCT) or the cribriform meshwork is made up of cells embedded in dense ECM. The JCT is considered to offer the major resistance to the aqueous humor outflow. This layer is adjacent to the endothelial cells forming Schlemm's canal, which provides approximately 10% of the outflow resistance. The ECM in the TM and the JCT undergoes continual remodeling to maintain normal resistance to aqueous humor outflow. It is believed that the TM is a major contributor of ECM proteins and evidence points towards increased ECM deposition in the outflow pathway in POAG. It is not clear how and from where the ECM components emerge to hinder the normal aqueous humor drainage. This review focuses on the involvement of the ECM in ocular hypertension and glaucoma and the mechanisms by which various ocular hypotensive drugs, both current and emerging, target ECM production, remodeling, and deposition.
Thermally labile components of aqueous humor potently induce osteogenic potential in adipose-derived mesenchymal stem cells
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We have recently reported that aqueous humor (AH), the fluid that nourishes the tissues adjoining the anterior segment of the eye, potently stimulates osteogenic potential in ASCs (Morgan et al., 2014). AH is a complex mixture of proteins, lipids, salts, and other small molecules (Cousins et al., 1991; De Berardinis et al., 1965; Duan et al., 2010; Edwards et al., 2014; Greiner et al., 1991; Iyer et al., 2012; Knisely et al., 1994; Lee et al., 1977; Rao et al., 2000; Russell et al., 2001; Tripathi et al., 1989). Several of these solutes have been previously implicated in osteogenesis, including ascorbate and glucocorticoids (Bellows et al., 1987, 1986; Herbertson and Aubin, 1995; Maniatopoulos et al., 1988; Tenenbaum and Heersche, 1982), growth-factor like lipids such as lysophosphatidic acid (LPA) (Liu et al., 2010), and the protein myocilin (Kwon et al., 2013).
Adipose-derived mesenchymal stem cells (ASCs) hold promise for use in cell-based therapies. Their intrinsic anti-inflammatory properties are potentially useful for treatments of inflammatory conditions such as uveitis, while their ability to differentiate along multiple cell lineages suggests use in regenerating damaged or degenerated tissue. However, how ASCs will respond to the intraocular environment is poorly studied. We have recently reported that aqueous humor (AH), the fluid that nourishes the anterior segment of the eye, potently increases alkaline phosphatase (ALP) activity of ASCs, indicating osteogenic differentiation. Here, we expand on our previous findings to better define the nature of this response. To this end, we cultured ASCs in the presence of 0, 5, 10, and 20% AH and assayed them for ALP activity. We found ALP activity correlates with increasing AH concentrations from 5 to 20%, and that longer treatments result in increased ALP activity. By using serum free media and pretreating AH with dextran-coated charcoal, we found that serum and charcoal-adsorbable AH components augment but are not required for this response. Further, by heat-treating the AH, we established that thermally labile components are required for the osteogenic response. Finally, we showed myocilin, a protein present in AH, could induce ALP activity in ASCs. However, this was to a lesser extent than untreated 5% AH, and myocilin could only partially rescue the effect after heat treatment, documenting there were additional thermally labile constituents of AH involved in the osteogenic response. Our work adds to the understanding of the induction of ALP in ASCs following exposure to AH, providing important insight in how ASCs will be influenced by the ocular environment. In conclusion, increased osteogenic potential upon exposure to AH represents a potential challenge to developing ASC cell-based therapies directed at the eye.

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The chemical composition of the human aqueous humour in normal and pathological conditions

J. biol. Chem.

J. biol. Chem.

J. biol. Chem.

Bull. Soc. Franc. Ophthal.

v. Graefes Arch. Ophthal.

Arch. Ophthal.

Physiology of the Ocular and Cerebrospinal Fluids

J. Physiol. Lond.

Arch. Augenheilk.

J. Physiol. Lond.