Vitreous gel
Eye

Author: Alessandro Marchese
Date: 08/02/2013

Description

Anatomy

The vitreous body is an highly hydrated extracellular matrix . It’s essentially composed by water (>98%), but it also consists of a complex network of macromolecules, vital for the maintenance of the gel structure.

It’s virtually acellular, except in the vitreous cortex and the basal vitreous, where we find some cells of the reticuloendothelial system, the hyalocytes, and a low concentration of fibroblasts. These cells are important for the synthesis of hyaluronic acid and the vitreous collagen.

Physiology

The vitreous gel has different functions, as:

  • Protecting the eye during mechanical trauma
  • Filling the space within the vitreous cavity, giving stability to the retina
  • Providing nutrients for the metabolic requirement of the lens and the retina
  • Coordinating eye growth
  • Maintaining transparency: it contains high concentration of ascorbic acid and others molecules that act as a neoangiogenesis inhibitors to maintain the transparency of the vitreous body. In fact neovascularization in adults is only found under pathological conditions which suggests that antiangiogenetic factors are present in the vitreous.

However, the vitreous gel can be almost completely substituted with replacement solutions without too drastic changes in ocular homeostasis.

Biochemical composition

The building network of vitreous gel is composed by collagens, glycosaminoglycans (GAGs) and non-collagenous structural proteins.

  1. GAGs are extracellular matrix polysaccharides that contains repeating disaccharide units. All GAGs, except hyaluronan, are synthesized attached to a protein core. The resulting macromolecule is called proteoglycan, that consists in a protein core and one or more GAGs chain attached.
    Hyaluronan. is the predominant GAG of vitreous. It’s a non sulphated molecule built from repeating disaccharide units (glucuronic acid and N-acetylglucosamine). It’s not uniformly distributed in the vitreous, the highest concentration is in the posterior vitreous cortex, then declines towards the anterior vitreous. Hyaluroan is an highly hydrated polyanion witch forms space filling networks, stabilizing the scaffold of collagen fibrils and cementing vitreous structure. Moreover it acts as a lubricant, as immunosuppressant, inhibits angiogenesis and contributes to tissue hydrodynamic because just small molecules can spread through its wide network.
    Sulphated GAGs are minor components of the vitreous gel. They are basically chondroitin sulphate (CS, glucuronic acid and N-acetyl-galactosamine) and heparan sulphate (glucuronic acid and N-acetylglucosamine), attached to different protein core. The two CS proteoglycans are type IX collagen and versican, which has a domain to bind hyaluroan. HS proteoglycans are major components of basement membranes, but the concentration in adult vitreous is very low.
  2. Collagen in the vitreous gel is mostly arranged into thin, uniform fibrils of mixed composition containing collagen types II,IX, and V/XI. The most represented, type II collagen (65%), forms fibrils and provides tensile strength to the vitreous scaffolding. Type IX collagen (25%) is not a fibrillar collagen and is present as a CS proteoglycan attached to collagen fibrils. Hybrid type V/XI collagen (10%), fibrillar, forms with type II collagen the core of the fibrils. Type VI collagen composes separate microfibrils, that links together the hyaluroan and the heterotypic collagen fibrils.
  3. Non-collagenous proteins in the vitreous include fibrillin, which is a component of the microfibrils composing the zonules (mutation of fibrillin-1 determines Marfan’s syndrome ). Opticin, a protein rich in leucine, is bound to surface of collagen fibrils. VIT1 is one of the latest identified structural proteins of the vitreous scaffold.
  4. Antioxidants: ascorbic acid is present within the vitreous in high concentrations, approximately nine times higher than the plasma levels. Such a elevated concentration may be justify by the ability of ascorbic acid to adsorb UV light, acting as a free-radical scavenger.

Structure

The difference between a gel vitreous and a liquid vitreous is the integrity of its microscopic structures. The collagen fibrils are a key element to maintain the gel form, as their digestion (for example by collagenase) liquefies the vitreous. Therefore, in the non-degenerate vitreous, the gel state is created and preserved by a thin network of heterogeneous collagen fibrils. But the collagen fibrils have a natural propensity to aggregate together. So, to prevent the conversion of the vitreous gel into a viscous liquid is necessary that the collagen fibrils don’t stick together but keep the distance from one another. In this process of short spacing the CS proteoglycans protruding from the collagen fibrils seemed to play an important role, keeping separate the fibrils, but it’s resulted they are not essential because their digestion doesn’t liquefy the vitreous gel. Instead appears to be important hyaluronan, which is able to interact with the collagen fibrils, even if this bond is very weak and could be broken by physical processes such as agitation. Another molecule with a likely role in the short-range spacing is opticin, a protein placed on the surface of the collagen fibrils. To maintain scattered these fibrils is also central a long-range spacing. The dilution operated by the water filling the vitreous cavity, especially linked to collagen and hyaluronan, it’s important in this way. However the digestion of the hyaluronan network (eg by hyaluronan lyasi) doesn’t destroy the gel structure, but just decreases the wet weight of the vitreous. Different macromolecules form the coat of the collagen fibrils and allow some sort of interactions between the fibrils, determining the skeleton of the vitreous gel. But on the other hand this coat prevent the lateral aggregation of the collagen skeleton, protecting the gel structure. The fibers of this collagen network are more numerous at the vitreous cortex and macromolecules on their surface interact with the inner limiting lamina of the retina, mediating vitro-retinal adhesion. This adhesion is tighter at the basal vitreous, weaker at the posterior cortex.

Vitreous aging and structural changes

With aging, progressively, part of the vitreous gel liquefies. This is a result of a lateral aggregation of the fibrils for a breakdown of those spacing mechanisms that block the natural tendency of the collagen fibrils to stick together. The collagen fibrils have a coat of different molecules on their surface, which may be damaged by aging or pathological processes. When collagen fibers aggregate together it’s very difficult to separate them from one another. They become thicker and can sometimes cast their shadows on the retina, determining floaters . With this process the collagen fibrils will result unevenly distributed in the vitreous and the areas lacking of fibrils will liquefy. The formation of liquid pockets usually begins in the central vitreous cavity and in front of the macula. Damages to the coating of the vitreous cortex determine a loss of vitro-retinal adhesion, predisposing to PVD (posterior vitreous detachment).

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