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    • Basic and Clinical Science Course - Excerpt
  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    2 Fundamentals and Principles of Ophthalmology

    Part IV: Biochemistry and Metabolism

    Chapter 9: Aqueous Humor, Iris, and Ciliary Body

    Composition of the Aqueous Humor

    Proteins

    As stated earlier, the tight junctions of the NPE, along with other structures, establish the blood–aqueous barrier, which prevents diffusion of plasma proteins from the ciliary stroma into the posterior chamber; nevertheless, plasma proteins do enter the aqueous humor, possibly through the root and anterior surface of the iris. Normal aqueous contains approximately 0.02 g of protein per 100 mL, as compared with the typical plasma level of 7 g per 100 mL. The most abundant plasma proteins identified in aqueous humor are albumin and transferrin, which together may account for 50% of the total protein content.

    In addition to the plasma proteins that enter the aqueous, there is compelling evidence that some proteins may be synthesized within the ciliary body and secreted directly into the aqueous humor. Molecular techniques (such as the screening of complementary DNA [cDNA] libraries constructed from intact human and bovine ciliary bodies) have enabled the isolation and identification of numerous protein-encoding genes. These studies, therefore, challenge the long-held view that plasma proteins in the aqueous humor are transported into the aqueous from outside the eye. Among the cDNA molecules isolated from the ciliary body are

    • C4, a component of the classical complement pathway that participates in immunemediated inflammatory responses

    • α2-macroglobulin, a carrier protein that is involved in proteinase inhibition, clearance, and targeting, as well as the processing of foreign peptides

    • apolipoprotein D, which binds and transports hydrophobic substances, including cholesterol, cholesteryl esters, and arachidonic acid (AA)

    • selenoprotein P, which has antioxidant properties

    Proteinases and inhibitors

    Several proteinases and proteinase inhibitors have also been identified in the aqueous humor. The proteinases include cathepsin D and cathepsin O, which are synthesized and secreted by the ciliary epithelial cells. Cathepsin D is involved in the degradation of neuropeptides and peptide hormones and has been found in high levels in the cerebrospinal fluid of patients with Alzheimer disease. Less is known about cathepsin O, which may be involved in normal cellular protein degradation and turnover.

    Of the proteinase inhibitors, α2-macroglobulin and α1-antitrypsin are perhaps the most extensively studied. An imbalance in equilibrium between proteinases and proteinase inhibitors could alter aqueous humor composition, which may cause disease (eg, glaucoma).

    Enzymes

    Activators, proenzymes, and fibrinolytic enzymes are present in the aqueous and could play a role in the regulation of outflow resistance. Both plasminogen and plasminogen activator are found in human and monkey aqueous, but only traces of plasmin have been reported.

    Neurotrophic and neuroendocrine proteins

    The ciliary epithelia, which are derived from neuroectoderm, are functionally similar to neuroendocrine glands elsewhere in the body. The ciliary body has neuroendocrine peptides and neuroendocrine processing enzymes. Bioactive neuroendocrine markers, identified through human ciliary body cDNA subtraction studies, include neurotensin, angiotensin, endothelins, and natriuretic peptides; these markers are known to have systemic vascular hemodynamic effects and, by implication, may have similar roles in IOP regulation or aqueous secretion. The neuroendocrine properties of the ciliary epithelium may determine the composition of the aqueous humor, the diurnal (circadian) rhythm of aqueous humor secretion and IOP, the ciliary blood flow, and the immune privilege status of intraocular structures.

    • Coca-Prados M, Escribano J. New perspectives in aqueous humor secretion and in glaucoma: the ciliary body as a multifunctional neuroendocrine gland. Prog Retin Eye Res. 2007;26(3):239–262.

    Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
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    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
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