Endothelium corneal

Exposure to UVB radiation has a profound effect on the corneal endothelium. Following exposure to UV radiation, the cornea swells, the extent and duration of which is directly related to the magnitude and duration of the exposure (Riley etal., 1987). At very high in vivo exposures, these authors reported a decrease in ascorbate concentration and an increase in protein content, which they suggested resulted from a breakdown of the blood-aqueous barrier. They concluded that UV radiation may cause or promote changes in the endothelium associated with ageing. 

Hull, D.S. and Green, K. (1989). Oxygen free radicals and corneal endothelium. Lens Eye Toxic Res. 6, 89-91. 

Fig. 4 Human corneal endothelium following 3-hour perfusion with lactated Ringer s solution (a) scanning electron micrograph (2100 x) (b) transmission electron micrograph (9100 x ). (Courtesy of H. Edelhauser.)... 

These effects, specialized for the geometries and materials properties of the collagen-rich stroma and sclera, have been calculated in a paper by Edwards and Prausnitz [197], They also modeled diffusion across the corneal endothelium assuming that the major path was... 

Intraocular irrigating solutions are required to be preservative-free to prevent toxicity to the internal tissues of the eye, particularly the corneal endothelium, lens, and retina [298,299]. These products are intended for single use only to prevent intraocular infections,... 

M Hirsch, G Renard, JP Faure, Y Pouliquen. (1977). Study of the ultrastructure of the rabbit corneal endothelium by the freeze-fracture technique Apical and lateral junctions. Exp Eye Res 25 277-288. 

ME Dowty, P Braquet. (1991). Effect of extracellular pH on cytoplasmic pH and mechanism of pH regulation in cultured bovine corneal endothelium Possible importance in drug transport studies. Int J Pharm 68 231-238. 

Geroski DH, Edelhauser HF. Quantitation of Na/K ATPase pump sites in the rabbit corneal endothelium. Invest Ophthalmol Vis Sci 25 1056-1060 (1984). 

Mannagh J, Irvine AR. Human corneal endothelium Growth in tissue cultures. Arch Ophthalmol 74 847-849 (1965). 

Corneal endothelium effects The effect of continued administration of brinzolamide and dorzolamide on the corneal endothelium has not been fully evaluated. 

Kuang K, Yiming M, Wen Q, Li Y, Ma L, Iserovich P, Verkman AS, Fischbarg 1 (2004) Fluid transport across cultured layers of corneal endothelium from aquaporin-1 null mice. Eixp Eye Res 78 791—798 Kuriyama H, Kawamoto S, Ishida N, Ohno 1, Mita S, Matsuzawa Y, Matsubara K, Okubo K (1997) Molecular cloning and expression of a novel human aquaporin from adipose tissue with glycerol permeability. Biochem Biophys Res Commun 241 53—58... 

Corneal epithelium Corneal stroma Corneal endothelium Anterior chamber... 

The flat endothelial cells of the scleral trabeculum succeed to the corneal endothelium. 

The inner layer of the corneal stroma is a dense membrane of collagen like the basal membrane of the monolayer of corneal endothelium. Descemets membrane is transparent with a thickness varying from 7 to 20 pm, according to the age of the individual. Conjunctiva and cornea host nerve endings of high density in the snperhcial and basal layers. The cornea at the limbns smoothly changes to sclera with interconnected nontransparent collagen hbrils. 

Fig. 6.1 HP diffusion within the cornea during an observation time of 30 min reaching the corneal endothelium (micrographs done by the IHT group of Prof. Dr. Kurz and Dipl. Ing. Spoler)...

Hudde, T., Rayner, S.A., Comer, R.M., Weber, M., Isaacs, J.D., Waldmann, H., Larkin, D.F.P. and George, A.J.T. (1999) Activated polyamidoamine dendrimers, a non-viral vector for gene transfer to the corneal endothelium. Gene Ther., 6, 939-943. 

The superficial two to three cell layers of the corneal and conjunctival epithelium are the main barrier for the permeation of topically applied compounds. In this rate-limiting cell layer, the transcellular permeation is dictated by the lipophilicity of the cell membrane whereas the paracellular permeation is limited by the paracellular pore size and density. Vesicular penetration (e.g., receptor- or endocytosis-mediated) of macromolecules across surface epithelium is possible [33], However, the proposed mechanism is energy consuming (e.g., incorporation into pinocytotic vesicles and phagosomes) and thus more feasible in cell lines with abundant intracellular energy sources like corneal endothelium and RPE [34-37]. 

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],... 

Tonjum, A.M. 1974. Vesicular transport of horseradish peroxidase across the rabbit corneal endothelium. Acta Ophthalmol (Copenh) 52 647. 

Fludde, T., et al. 1999. Activated polyamidoamine dendrimers, a non-viral vector for gene transfer to the corneal endothelium. Gene Ther 6 939. 

Descemet s membrane covers the posterior surface of the stroma. It is a single-cell layer, 5-10 pm thick, and also composed of collagen. The corneal endothelium, a single-cell layer lining the posterior surface of the stroma, is rich in phospholipids, permeable to lipid-soluble materials, and almost impermeable to ions. 

A single layer of flat hexagonal cells of the corneal endothelium covers the posterior corneal surface and hydrates the cornea. The corneal endothelium can allow diffusion of molecules of dimensions up to 20 nm.65 The stroma has a highly organized hydrophilic tissue structure that comprises 90 percent of cornea.63 It has an open structure that can allow molecules up to 500,000 Da in size to pass through. However, the stroma may be a diffusion barrier to lipophilic drugs.65,84 Drug-melanin interactions such as the one with timolol can form a barrier and reduce bioavailability.85... 

In addition to the work presented here, several alternative viral-vectored approaches have been reported recently. An adeno-associated viral vector (AAV) encoding the soluble VEGF receptor 1, sFlt-1, shows promise for long-term inhibition of two types of ocular neovascularization (Lai et al., 2002). This vector, when injected into the anterior chamber, resulted in expression in both the corneal endothelium and iris pigment epithelium and reduced corneal NV by 36%. Subretinal injection of the same vector reduced choroidal NV subsequent to laser lesions around the optic nerve. These results suggest that a secretable factor expressed in one or more transduced cell populations can be elfective in the control of ocular NV occurring in a disparate cell population. 

A 50-year-old woman with schizophrenia had a 1-year history of gradual deterioration of vision in both eyes. For several years she had been taking chlorpromazine 300 mg/day, trifluoperazine 10 mg/day, and trihexyphenidyl 4 mg/day. Slit lamp examination showed fine, discrete, brown refractile deposits on the corneal endothelium in both eyes, and characteristic bilateral stellate cataracts with dense, dust-like brown-yellow granular deposits were noted along the suture lines in the anterior pole of the lens and obscured the visual axis. 

A 59-year-old woman who for 20 years had taken chlorpromazine up to 1200 mg/day (mean dose 400 mg/day) gradually developed blurred vision in her left eye. Slit-lamp biomicroscopy showed multiple fine creamy-white deposits on her corneal endothelium and anterior crystalline lens capsule bilaterally. Microstructural analysis of the corneal endothelium showed that there were no abnormalities in cellular morphology resulting from these deposits. 

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