Stroma, corneal, structure

As another extracellular component in the cornea, the Bowman s layer is an acellular and amorphous band between the corneal epithelium and stroma. The layer is about 8-12 [im thick and consists of randomly arranged collagen fibers (types I and III) and proteoglycans. The physiological function of Bowman s layer is not yet completely understood, since not all animal species exhibit this membrane in the corneal structures, but an important role in the maintenance of the corneal epithelial structure is expected or probable, since a damaged Bowman s membrane usually results in scarring during wound repair [16],... 

In another approach, Parnigotto and coworkers reconstructed corneal structures in vitro by using corneal stroma containing keratocytes to which corneal epithelial cells from bovine primary cultures were overlaid [73], However, this particular corneal model did not contain an endothelial layer. This model was histochemically characterized and the toxicity of different surfactants was tested using MTT methods. This stroma-epithelium model has been reported to show a cornea-like morphology, where a multilayered epithelial barrier composed of basal cells (of a cuboidal shape) and superficial cells (of a flattened shape) is noted. Furthermore, the formation of a basement membrane equivalent and expression of the 64-kDa keratin were reported, indicating the presence of differentiated epithelial cells. The toxicity data for various surfactants obtained with this model correlate well with those seen by the Draize test [73], However, this corneal equivalent was not further validated or used as a model for permeation studies. 

One of the key parameters for correlating molecular structure and chemical properties with bioavailability has been transcorneal flux or, alternatively, the corneal permeability coefficient. The epithelium has been modeled as a lipid barrier (possibly with a limited number of aqueous pores that, for this physical model, serve as the equivalent of the extracellular space in a more physiological description) and the stroma as an aqueous barrier (Fig. 11). The endothelium is very thin and porous compared with the epithelium [189] and often has been ignored in the analysis, although mathematically it can be included as part of the lipid barrier. Diffusion through bilayer membranes of various structures has been modeled for some time [202] and adapted to ophthalmic applications more recently [203,204]. For a series of molecules of similar size, it was shown that the permeability increases with octa-nol/water distribution (or partition) coefficient until a plateau is reached. Modeling of this type of data has led to the earlier statement that drugs need to be both... 

Microscopically, the cornea shows a rather simple and multilayered structure that can be divided into six layers the epithelium, basement membrane, Bowman s layer, stroma, Descemet s membrane, and endothelium. The corneal tissue consists of three different cell types epithelial cells, keratocytes (corneal fibroblasts), and endothelial cells. The outermost corneal surface is covered with the preocular tear film, which is functionally associated with the cornea. The epithelial surface must be kept moist and smooth, a role played by the tear film in conjunction with a spreading function of the eyelids during blinking motions. Furthermore, the tear film provides a protection against infectious agents that may gain access into the eye. 

These vessels end in arcade-like structures at the limbus. The corneal stroma is made of three different main layers that differ in density of collagen and type of packing. The Bowman s membrane of the anterior stroma is part of the basal membrane of the corneal epithelium and accounts for 5% of the thickness of the central 500-600 pm cornea. The corneal stroma consists of highly ordered, horizontally organized and noninterconnected coUagen I and X fibriUae that are kept in a hydrated state with a water content of 72-78% and an osmolarity of 420 mOsmol/kg [1]. 

Langefeld, S., Reim, M., Redbrake, C., Schrage, N.F. The corneal stroma, an inhomogenous structure. Graefes Arch Clin Exp Ophthalmol 235(8), 480 85 (1997)... 

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]. 

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... 

Figure 3.4. Structure of cornea. The structural components of cornea include epithelium, corneal stroma, collagen lamellae and Bowman s and Descemet s membranes.

The outer surface of the cornea is covered with a smooth layer of stratified corneal epithelium (Figure 3.4). The lower layer of cells is columnar in shape and rests on a basement membrane that sits on top of a thick limiting structure termed Bowman s membrane derived from the corneal stroma below. The corneal stroma is composed of parallel bundles of collagen fibrils termed lamellae and rows or layers of branching corneal fibroblasts termed keratocytes. The posterior of the cornea is covered with a low cuboidal epithelium with a wide basement membrane (Descemet s membrane) and rests on the posterior portion of the corneal stroma. The corneal epithelium is normally under tension due to the pressure that is present in the anterior chamber just behind the cornea. The intraocular pressure is between 10 and 20 mm of mercury and is enough to cause the cornea to contract about 5% when it is excised from the eye. Therefore this pressure must be transferred between epithelium via cell-cell junctions. 

The stroma makes up approximately 90% of the corneal thickness and is mainly composed of hydrated collagen fibrils. It is highly hydrophilic, porous, and can be considered as an open structure, as it allows free passage of hydrophilic substances with a molecular weight below 500,000Da but acts as a diffusion barrier to all lipophilic drugs [4,12],... 

Histologic cross-section of the cornea reveals five identifiable layers epithelinm. Bowman s layer, stroma, Descemet s membrane, and endothelium. Fluid surrounds the cornea in the forms of the tear film in front and the aqneons behind. The various corneal layers combine to form a structure that is approximately 633 mcm thick at the inferior periphery, 673 mcm at the superior periphery, and 515 mcm thick centrally. The adult corneal diameter measmes 11 to 12 mm horizontally and 9 to 11 mm vertically, creating a horizontally oriented ellipse. The radius of ciuvature of the central 3-mm optical zone ranges between 7.5 and 8.0 mm. 

The Stroma, or substantia propria, is composed of around 90% of the corneal thickness that contains about 85% water and about 200-250 collagenous lamellae. The lamellae provide physical strength while permitting optical transparency of the membrane. The hydrophilic solutes diffuse through the stroma s open structure. 

The corneal epithelium (epithelium cornea anterior layer) is made up of epithelial tissue and covers the front of the cornea (Figure 51.4). It acts as a barrier to protect the cornea, resisting the free flow of fluids from the tears, and prevents bacteria and also therapeutic drugs from entering the epithelium and corneal stroma. The epithelium of the cornea consists of five to six layers of cells packed closely and connected by tight junctions. The cornea is composed of five layers epithelium, Bowman s membrane, stroma, Descemet s membrane, and endothelium, each of alternating polarity. This sandwich-like structure makes the cornea a crucial barrier to most lipophilic and hydrophilic drugs. To penetrate these layers, optimal lipophilicity for the permeant corresponds to log D values of 2-3. °... 

FIGURE 38.2 Structure of the cornea. Left Representative histology of a rabbit corneal section. Scale bar is 40 pm. Right Transmission electron microscopy of a rabbit eye, demonstrating the ultrastructure of different corneal layers. Scale bar is 4 pm. Labels ce comeal epithelium b basal epithelial cell bll Bowman s-like layer as anterior stroma k keratocytes ps posterior stroma dm Descemet s membrane endo comeal endothelium. Unpublished data. 

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