The greatest difference between human AH and plasma resides in the very low protein and high ascorbate concentration in the aqueous tab. The levels of these constitutes are thought to be involved in the development of several eye diseases , and investigating the AH will facilitate generation of new hypotheses regarding the etiology of such pathologies .
In the article, there were pointed out the most frequent ocular pathologies that cause blindness: glaucoma, uveitis, and diabetic retinopathy, and their changes in the AH's composition that can be named biomarkers. The variations in AH may be relevant for future diseases treatment. All three pathologies are a significant public health problem, being the leading cause of irreversible visual loss.
Glaucoma is a group of optic neuropathies characterized by progressive degeneration of retinal ganglion cells and appears at subjects older than 40 years. It affects more than 70 million. Uveitis is an inflammatory disease affecting the uveal layer of the eye. Diabetic retinopathy is another leading cause of vision-loss globally, affecting adults aged years. Of an estimated million people with diabetes mellitus worldwide, approximately one third have signs of diabetic retinopathy .
In most glaucomas, it was established an increased resistance through the trabecu-lar meshwork that contributes to elevated IOP and influence on AH's composition . Diabetes mellitus is associated with problems of general circulation. Ocular effects are dependent on the duration of diabetes, the age of the patient, and the severity of retinopathy.
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They include changes in AH dynamics, IOP, aqueous flare, permeability of blood-ocular barrier, and retinal vasculature [22, 26]. Uveitis is characterized by inflammation that can cause iris atrophy and secondary glaucoma in some patients. Several studies pointed out different changes in AH due to the increased permeability of the blood-aqueous barrier [5, 26]. The exact number of human AH constitutes is unknown, and it is possible that tens if not hundreds of components exist in the AH and many of these could fall below current detection limits and difficulty in collecting a big quantity for the biochemical exam due to the small eye's chambers.
Specific markers for main pathologies represent nowadays an important field of research. Therefore, it was decided to select the most important constitutes from AH for glaucoma, diabetic retinopathy and uveitis, and to analyze their concentration, properties changes. So, one of the main constitutes of AH is ascorbic acid Vitamin C with a concentration about 15 times greater in the AH than in plasma has the role of antioxidant, protecting the eye from the deleterious effects of free radicals and toxins [10, 21, ].
The concentration of ascorbate is about 15 times greater in the AH than in plasma, suggesting that vitamin C may protect against harmful factors within the eye [10, 41]. It was detected in cornea, AH, lens, vitreous humor, and retina [41, 44].
However, Vitamin C concentrations in AH are lower in patients with various ophthalmic diseases. At the patients with age-related cataract from 50 to 70 years old the concentration of vitamin C in AH decreases suggesting that this phenomenon may play a role in susceptibility to cataract formation in older people [44, 45]. Vitamin C concentrations are lower in patients with exfoliation syndrome and glaucoma .
The endotoxin-induced ocular inflammation in uveitis caused a decrease in the concentration of ascorbic acid in the AH . Diabetic patients have an imbalance between free radical generation and antioxidant defense vitamin C, vitamin E which may play a role in the progression of diabetic retinopathy .
The low concentration of proteins in AH 0,02g at ml comparative to plasma concentration of 7g at ml is essential for maintaining the optical transparency , this is due to the blood-aqueous barrier. AH comprises many proteins with various roles and important biological functions. The exact number and concentration of human AH proteins are unknown, as it is supposed that tens if not hundreds of lower abundance proteins exist in the AH and many of these could fall below current detection limits .
Most of the proteins identified had catalytic, enzymatic, and structural properties . The most abundant proteins found in normal AH are albumin, immunoglobulin G IgG , transferrin, haptoglobin and antitrypsin that represent the major ones [32, 33]. Amount of proteins and cells in AH was observed after surgery, paracentesis, or uveitis . In Prata T. Although, it is considered that the alterations in the protein composition of AH trigger signaling molecules that modify the trabecular meshwork and increasing resistance to outflow and induce glaucoma . Grus E. It might play a role in the onset of glaucoma since it has been shown to form amyloid deposits increasing intraocular pressure by the particles that could cause outflow obstructions .
The pathogenesis of uveitis is associated with abnormal expression of some proteins and aberrant regulation of multiple signaling pathways . The blood-aqueous barrier breaks down  and the composition and concentrations of proteins in aqueous are similar to that of plasma . In diabetic patients, the proteome composition of AH suffers change too [67, 68]. Chiang S. There were detected at lower levels - SERPINF1 encoded protein is secreted and strongly inhibits angiogenesis and prostaglandin-H2 D-isomerase PTGDS - involved in development and maintenance of the blood-retina, blood-aqueous humor barrier compared to control [68, 69].
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These altered proteins are involved in in-. Other important protein found in diabetic AH that has an important role in angiogenesis is vascular endothelial growth factor VEGF [71, 72]. Data from several studies support the generally accepted supposition that the VEGF level in the aqueous liquid collected from the anterior chamber adequately reflects the VEGF activity in retinal tissues [72, 73]. Glucose levels in AH correlate with blood glucose levels . It is a component of the AH due to the process of diffusion. Davies P. There were determinate differences between non-diabetic and diabetic patients.
The glucose levels in non-diabetic patients were 5. In addition, the glucose level influences the IOP intraocular pressure in patients with uncontrolled diabetes that was significantly higher [79, 80]. The mechanism is still unclear, but in vitro studies suggested that high glucose conditions could induce excess extracellular matrix synthesis by trabecular meshwork cells. Accumulation of extracellular matrix in the trabecu-lar meshwork blocks the aqueous outflow [81, 82].
Glucose levels of AH in ocular inflammations as iritis, keratitis and corneal ulcer are elevated, according to Alaerts et al. There is no evidence about the concentration of glucose in glaucoma. Anyway, the changes in the most important constitutes of the AH involve modifications in the other components ions, amino acids etc. All the biochemical researches made on specific marker in the AH for eye pathologies are developing. This study reveals significant variations in the differentially abundant changes in human aqueous humor that may be relevant for future diseases treatment in order to get favorable outcomes in patients.
The aqueous humor proper composition is important in the regulation of the homeo-stasis of the ocular tissues. Every pathology leads to changes to aqueous humor. They influence physiological properties and cause pathological conditions in the eye. The specific identification of these markers will aid in understanding various eye diseases of the anterior segment such as glaucoma, uveitis and diabetic retinopathy. Other areas for future study include determining differences in aqueous humor constitutes levels among patients in different age groups.
Distinctive and pervasive alterations in aqueous humor protein composition following different types of glaucoma surgery. Mol Vis. LC-MS-based metabolic fingerprinting of aqueous humor. J Anal Methods Chem. Ringvold A. Exp Eye Res.
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