Permeability cornea

Li, Y, Liu, J., Pan, D. and Hopfinger, A.J. (2005) A study of the relationship between cornea permeability and eye irritation using membrane-interaction QSAR analysis. Toxicol. Sci., 88, 434-446. 

CoRNFAL Permeability Measurements The measurement of effects of substances on cornea) permeability to fluorochromes can be used as a means for the early detection of corneal injury and is a predictor of eye irritating potential (Ballanlyne, 1999a Elter and Wildhabcr, 19R5 Maurice and Brooks, 1995). 

O Camber. P Edman. Intluence of some pre.servatives on the cornea) permeability of piktearpine and dexamethasone, in vitro, int J Pharm. 19 229-2,14. 1987. 

The GSH reductase inhibitor l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) also promotes corneal swelling in the isolated cornea. The addition of GSH prevents the action of BCNU as the cornea needs a constant supply of NADPH for maintaining adequate concentrations of reduced glutathione for the detoxification of hydrogen peroxide. It has been shown that hydrogen peroxide and BCNU primarily affect the permeability of the endothelial cells rather than the active processes transporting sodium and chloride ions across the membrane (Riley, 1985). 

There is growing evidence implicating Na+-dependent solute transporters and intracellular as well as extracellular Ca2+ in the physiological regulation of the paracellular pathway [81,203,204], Such modulation of paracellular permeability is especially important for drugs such as peptides and oligonucleotides that exhibit poor permeability characteristics across both the cornea and the conjunctiva [150,152,154,155], In addition, ion transporters such as Cl and Ca2+ channels have been implicated in macromolecular transport (see Sections IV.B.2 and IV.B.4). In the following discussion, some key ion transport processes and their possible roles in solute transport across epithelial tissues are summarized. 

The effects of D-glucose observed in vivo are not well reproduced in vitro. Madara [203] reported that cytoskeletal contraction and enhanced paracellular permeability were observed only in an in situ perfusion preparation and not in an isolated tissue preparation. Although its in vivo effect was not tested, 25 mM D-glucose, an effective concentration in the jejunum [47], failed to enhance the in vitro transport of sotalol (log PC = -0.62), atenolol (log PC = 0.16), or nadolol (log PC = 0.93) across the isolated conjunctiva [213], For a similar reason and possibly due to the absence of a Na+-glucose cotransporter in the cornea, 25 mM D-glucose was ineffective in increasing the corneal transport of these three drugs. 

KM Morimoto, T Nakai, K Morisaka. (1987). Evaluation of permeability enhancement of hydrophilic compounds and macromolecular compounds by bile salts through rabbit corneas in vitro. J Pharm Pharmacol 39 124-126. 

DM Maurice. (1951). The permeability to sodium ions of the living rabbit cornea. J Physiol 112 367-391. 

Y Rojanasakul, JR Robinson. (1991). The cytoskeleton of the cornea and its role in tight junction permeability. Int J Pharm 68 135-149. 

Swan, K.C. and White, N.G. (1972). Corneal permeability (1) factors affecting penetration of drugs into the cornea. Amer. J. Ophthalmol. 25 1043-1058. 

Several in vitro methods, including the hen s egg chorioallantoic membrane test (HET-CAM) the bovine cornea opacity and permeability assay (BCOP) and the isolated rabbit eye (IRE) test, have gained regulatory acceptance in Europe for the classification of severe eye irritants. Many companies are using such techniques successfully to reduce in vivo testing during development. ... 

The sclera is the outer white tough part of the eye, which is an important structural element, with the site of insertion of extraocular muscles. It covers 80% of the exterior surface and is white and nontransparent. It borders the transparent cornea at the pars planar. The sclera is divided into three layers episclera, stroma, and lamina fusca. Only a limited number of blood vessels, originating from arteriolar branches of the anterior ciliary vessels, are found and superficial vessels are mainly confined to the loose outer episclera. Scleral permeability approximates that of the corneal stroma and has been shown to be permeable to solutes up to 70 kDa in molecular weight [14]. 

After permeation through the corneal epithelium, molecules should then permeate through the hydrophilic corneal stroma and the corneal endothelium before reaching the aqueous humor. Thus, while the corneal epithelium favors the penetration of lipophilic compounds, the hydrophilic stroma favors the permeation of hydrophilic compounds. The corneal endothelium monolayer is not sealed by paracellular zonulae occludentes. Consequently this layer has only a minimal effect on the overall permeability of the cornea. Overall, the cornea as a whole is tailored to allow the permeation of moderately lipophilic compounds (close to log P = 2) [40], On the contrary, the reported optimal lipophilicity for compounds penetrating through an isolated epithelial layer of the cornea was around log P=4 [41],... 

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