Aqueous humor secretion

Except for dorzolamide and brinzolamide, carbonic anhy-drase inhibitors are administered systemically. Carbonic anhydrase is an enzyme found in many tissues of the body, including the eye Inhibition of carbonic anhydrase in Hie eye decreases aqueous humor secretion, resulting in a decrease of IOE These drugs are used in the treatment of elevated IOP seen in open-angle glaucoma... 

Carbonic anhydrase plays an important role in the secretion of aqueous humor [1,2]. This enzyme was first demonstrated to be present in the ciliary processes of the rabbit, and its presence was later confirmed in human ciliary processes [3,4]. Carbonic anhydrase is responsible for the generation of bicarbonate anions which are secreted from the ciliary process into the posterior chamber, with sodium being the counter ion. Inhibition of carbonic anhydrase in the ciliaiy processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The role of the enzyme in aqueous humor secretion has been reviewed in detail by Maren [1]. 

Orally administered carbonic anhydrase inhibitors lower the intraocular pressure of glaucoma patients, however they induce a number of intolerable side effects associated with extraocular inhibition of the enzyme [5,6]. Thus, much research has been directed towards the search for a topically effective agent. Several compounds have been synthesized since the 1980 s in Merck Sharp Dohme Research Laboratories, and have been found to be topically active in man [7]. Unfortunately, many of these compounds were not very soluble. Attempts to obtain an active carbonic anhydrase inhibitor with good solubility resulted in the synthesis of Dorzolamide hydrochloride [8,9], which was first made available for pharmacological evaluation in 1987. Like other carbonic anhydrase inhibitors sulfonamides (such as acetazolamide, ethoxzolaniide, and methazolamide) dorzolamide is an inhibitor of human carbonic anhydrase isoenzymes I, II, and IV. In contrast to the other sulfonamides, dorzolamide is a potent inhibitor of isoenzymes II and IV, and a weak inhibitor of isoenzyme I [ 10]. Isoenzyme II is thought to play a major role in aqueous humor secretion. 

MecHanism of Action An ophthalmic agent that inhibits carbonic anhydrase. Decreases aqueous humor secretion. Therapeutic Effect Reduces intraocular pressure (lOP). 

When limited to narrow borders, higher tearing and increased aqueous humor secretion are the only ways to increase the buffering capacity of the eye. 

Millar, C., and P.L. Kaufman. 2002. Aqueous humor secretion and dynamics. In Duane s ophthalmology on CD-ROM, Foundations of Clinical Ophthalmology, vol. 2, eds. W. Tasman and E.A. Jaeger. Philadelphia Lippincott Williams Wilkins, chap. 6. 

CAIs reduce lOP by decreasing ciliary body aqueous humor secretion. CAIs appear to inhibit aqueous production by blocking active secretion of sodium and bicarbonate ions from the ciliary body to the aqueous humor. Topical CAIs such as dorzolamide and brin-zolamide are well tolerated and are indicated for monotherapy or adjunctive therapy of open-angle glaucoma and ocular hypertension. Relatively specific inhibitors of carbonic anhydrase enzyme II such as dorzolamide and brinzolamide reduce lOP by 15% to 26%. 

Complex organ control— the eye The eye contains multiple tissues with various functions, several of them under autonomic control (Figure 6-5). The pupil, discussed above, is under reciprocal control by the SANS (via alpha receptors) and the PANS (via muscarinic receptors) acting on two different muscles in the iris. The ciliary muscle, which controls accommodation, is under primary control of muscarinic receptors innervated by the PANS, with insignificant contributions from the SANS. The ciliary epithelium, on the other hand, has important beta receptors that have a permissive effect on aqueous humor secretion. 

The (7 )-HETEs are known to have potent biological effects however, it is typically unknown whether COX, LOX, or CYP enzymes are responsible for (7 )-HETE generation. 12(7 )-HETE formed in corneal epithelium is believed to be of CYP origin and inhibits the Na /K -ATPase to regulate ocular transparency and aqueous humor secretion [86]. Inhibition of the Na /K -ATPase by 12(7 )-HETE also increases urinary sodium... 

Maren, T.H. Jankowska, L. Sanyal, G. Edelhauser, H.F. (1983). The transcorneal permeability of sulphonamide carbonic anhydrase innhibitors and their effect on aqueous humor secretion. Experimental Eye Research, 36,457-480. 

Dorzolamide Hydrochloride is an inhibitor of human carbonic anhydrase II. The inhibition of carbonic anhydrase in the ciliary processes of the eye decreases the secretion of aqueous humor, with a resulting reduction in intraocular pressure. The drug is formulated as an ophthalmic solution, and administered topically as eyedrops. 

T.H. Maren, The Development of Ideas Concerning the role of Carbonie Anhydrase in the Secretion of Aqueous Humor Relation to the Treatment of Glaueoma , in Glaucoma Applied Pharmacology in Medical Treatment,. S.M. Drance and A.H. Neufeld, eds., Grune and Stratton, Inc., Orlando, 1984, pp. 325-355. 

Glaucoma Timolol and other ocular P-blockers are used to treat glaucoma. Propranolol is effective in diminishing intraocular pressure in glaucoma. This occurs by decreasing the secretion of aqueous humor by ciliary epithelium. It neither affects the ability of eye to focus for near vision, nor changes pupil size. Used in chronic cases only. 

Structures of the anterior chamber of the eye. Tissues with significant autonomic functions and the associated ANS receptors are shown in this schematic diagram. Aqueous humor is secreted by the epithelium of the ciliary body, flows into the space in front of the iris, flows through the trabecular meshwork, and exits via the canal of Schlemm arrow). Blockade of the 13 adrenoceptors associated with the ciliary epithelium causes decreased secretion of aqueous. Blood vessels (not shown) in the sclera are also under autonomic control and influence aqueous drainage. 

At present, the major clinical applications of acetazolamide involve carbonic anhydrase-dependent HC03 and fluid transport at sites other than the kidney. The ciliary body of the eye secretes HC03 from the blood into the aqueous humor. Likewise, formation of cerebrospinal fluid by the choroid plexus involves HC03 secretion. Although these processes remove HC03 from the blood (the direction opposite of that in the proximal tubule), they are similarly inhibited by carbonic anhydrase inhibitors. 

All burnt comeal stroma show lower osmolarity due to the loss of ions by continuous rinsing. The higher osmolar Diphoterine adds some ions to the burnt corneal stroma, but its osmolarity is still much lower than the one of the aqueous humor. It is obvious that there is no change in osmolarity in aqeous humor in healthy and in burnt eyes due to autoregulation of this milien by the ciliary body secretion. The considerable differences in tissue osmolarity indicate that there will be a strong fluid uptake into the comeal tissue, resluting in opacity. This indicates a severe water uptake and a lack of the endothelial pumping function. 

AQP-1 Fluid reabsorption in proximal renal tubule secretion of aqueous humor in eye and cerebrospinal fluid in central nervous system water homeostasis in lung... 

The ciliary body, situated posterior to the iris, performs several functions. It connects the anterior part of the choroid to the circumference of the iris, and contains the ciliary muscles necessary for accommodation. The ciliary body secretes aqueous humor into the posterior together with nutrients to nourish the lens. In the ciliary body, melanin is located only in the outer pigmented epithelium [24]. Aqueous humor is actively secreted and passively filtered by the ciliary body. Although the rate of secretion is about 2 pL/min the same volume is drawn-off via Schlemm s canal from where it is conducted into veins [25]. 

The eye globe is a hollow structure filled anteriorly by the aqueous humor and posteriorly by the vitreous. The aqueous humor (Figure 24.1) is continuously formed by the ciliary body. It is secreted into the posterior chamber from which it passes through the pupil into the anterior chamber and is drained at the anterior chamber periphery. Due to the blood aqueous barrier formed by zonulae occludentes of the nonpigmentary ciliary epithelium, macromolecules such as proteins can pass to the aqueous in very small quantities, regardless of their plasma concentrations. In humans, the aqueous humor protein level is around 20 mg/100 mL, less than 0.5% of the normal plasma total protein levels (Table 24.1) [22]. In the human eye, the rate of aqueous formation is around 2.5 pL/min, whereas in the case of rabbit eye it is... 

Glaucoma is a disease characterized by increased intraocular pressure. Muscarinic stimulants and cholinesterase inhibitors reduce intraocular pressure by causing contraction of the ciliary body so as to facilitate outflow of aqueous humor and perhaps also by diminishing the rate of its secretion (see Figure 6-9). In the past, glaucoma was treated with either direct agonists (pilocarpine,... 

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