4. The collapse process of the epithelial cell

　Although an epithelial cell which has changed to a balloon cell does not break up yet, it is virtually dead. This dying epithelial cell attempts to change to a fiber cell. Next, the cells slowly begin to die. They begin autolysis. When it occurs, lysosomal enzymes are released into the cell itself.

Lysosome: One of the minute bodies seen with the electron microscope in many types of cells, containing various hydrolytic enzymes and normally involved in the process of localized intracellular digestion.¹

Injured epithelial cells begin to be decomposed by lysosomal enzymes. Then those cells travel the course, as if they have grown normally and go on their own way. After that, they become fragments of the cells, and they are decomposed completely at the end. Those decomposed substances develop into wedge-shaped opacity gradually. Cogan observes very correctly the collapse process of the epithelial cell, or the balloon cell.

5.  Essential liquefaction

　This is the 3rd of three types of histopathologic changes in cortical cataract which David G. Cogan listed. (Fig.4-11)

　After the balloon cell formation, the next change begins. Cogan writes as follows.

  “An alternative manifestation of corticolysis， less common than that associated with morgagnian globules，is essential liquefaction of the lens substance. Like the morgagnian globules，it also occurs in sharply circumscribed zones at intermediate depths of the cortex，but the zones are filled with granular debris and fascicles of disintegrating fibers rather than globules (Fig.6). It appears to be a rapid and direct process of corticolysis rather than a transition by way of morgagnian globules or balloon cells. This type of change may correspond to the "water clefts" seen with the biomicroscope in rapidly advancing cataracts.⁴”

Liquefaction: The conversion of a material into a liquid form.¹

　This is the 2nd stage of the lens collapse. Cogan describes the sight that lysosomal enzymes released from dying epithelial cells decompose the cells themselves. Cogan is not aware that the cause of corticolysis is the cell death by the PRESSURE. Though, he observes the advance process of cataract precisely. As he says, this essential liquefaction corresponds to the “water clefts.” The essential liquefaction grows to the water cleft. The collapse of the lens develops from the state of the balloon cell to the water cleft in which cells are decomposed by lysosomal enzymes.

6. Formation of eosinophilic globules (Morgagnian globules)

　This is the 2nd of three types of histopathologic changes in cortical cataract which Cogan listed. He describes as follows. (Fig.4-12)

“Whereas balloon cells predominate in the subcapsular regions， the clusters of what are called morgagnian globules are found predominantly at intermediate depths of the cortex. The globules consist of eosinophilic discs without cell walls or other structures that are obvious by light microscopy (Fig.5). The cluster areas are bordered by lens fibers that appear，by contrast，remarkably normal. The globular configuration is probably an artifact of fixation. What appear microscopically as clear spaces between the globules undoubtedly result from shrinkage of the amorphous lens substance. This substance presumably corresponds in life to the opaque spokes of cortical cataracts.⁴”

Eosinophilic: Readily stainable with eosin.¹

Morgagnian globules and eosinophilic discs might be substances stuck together temporarily after the balloon cell has decomposed into minute substances via lysosomal enzymes.

This is the 3rd stage of the lens collapse. In this state, since the cell membrane and cell components have decomposed completely, they do not retain even the shape of the fragment of the cell.

<The water cleft>

　After the 3rd stage, the early stage of the water cleft begins. This becomes larger by degrees. Afterwards the water cleft begins to give rise to new collapses of the fiber cells. Water clefts enlarge more; meanwhile, opaque substances begin to be made. Those opaque substances will be accumulated between the bundles of fiber cells, and then those substances gradually grow into larger wedge-shaped opacities. This is the wedge-shaped cataract.

　The PRESSURE put on the lens equator travels in the wedge-shaped opacity from the equator to the anterior polar part of the cortex. The wedge-shaped opacity is a mass of opaque substances. The power of the opacity works on lens fibers destructively as Pressure[b].

  <The collapse of the epithelial cell stops temporarily.>

　The cells seem to continue to be crushed at the equator. However, it is not so. Ralph Michael et al. observed that phenomenon and wrote as follows.

“Panel of dark-field micrographs of old human donor lenses, illustrating the presence of mild (A and B) and advanced (D and E) cortical opacities along the entire circumference of the lens. Photographs taken before lens fixation. In D and E, the opacities extend as spokes into the pupillary space and will likely have affected the vision of the donors. The space between the outer limit of the opaqueness and the lens circumference is relatively transparent, becoming especially evident at higher magnifications of the boxed areas in (B) and (E) (C and F, respectively).¹⁷” (Fig.4-13)

　These phenomena are common changes in wedge-shaped cataracts. Cogan describes also these phenomena as follows, which I quoted before. “Some of these clusters of balloon cells may become displaced into the deeper cortex by the generation of normal overlying fibers.”

Those phenomena indicate that epithelial cells cannot continue being destroyed in succession. After the water cleft has been formed, no hardened layer of fiber cells is under the equator. If fiber cells under the epithelial cells have not made a layer of sufficient thickness, new collapses of the epithelial cells do not occur. In such circumstances, if the capsule puts pressure on the epithelial cells on the equator, the underlying water cleft cannot receive the pressure. The water cleft only diffuses the pressure deep into the lens. This is because the water cleft is soft, not hard. The collapse of the epithelial cell stops temporarily, until the next layer of hardened fiber cells grows. After a hardened layer of fiber cells has grown enough, the collapses of epithelial cells start again.

In these photographs, normal epithelial cells and normal fiber cells are not visible. Only insoluble proteins and insoluble aggregates in the water cleft are visible.

<The structure of the lens>

The water cleft in an advanced stage, is a wedge-shaped opacity. It begins to destroy surrounding cells by “Pressure[b]1” and “Pressure[b]2.” What we named “Pressure[b]1”, works as the power which slides a layer of fiber cells on the other layer. What we named “Pressure[b]2”, works as the power which drives an apex of wedge-shaped opaque substances into an inter-layer space of fiber cell layers.

Pressure[b]1 and Pressure[b]2 work depending on a characteristic structure of the lens. (Fig.4-14) Gray's Anatomy describes this as follows, “it is clear that fibres pass from the apex of an arm of one suture to the angle between two arms at the opposite pole，as shown in the colored segments. Intermediate fibres show the same reciprocal behaviour， ending nearer to one pole， where they start further from the other， and so on.¹⁸”

The lens fiber cells form a bundle, or a layer. If this bundle of hardened fiber cells moves due to the PRESSURE, the bundle causes Pressure[b]1. By this power the bundle slides on the neighboring layer of fiber cells. The bundle which moves is the wedge-shaped opacity.

The fiber cells connect to each other by interceller connection. (Fig.4-15) Edward Cotlier describes this as follows.

“The membranes of the fibers have side digitations that result in fiber interlocking¹⁹.”

When the wedge-shaped opacity moves, the slide of the wedge-shaped mass breaks the interceller connection, or the side digitation of the cells in the neighboring bundle.

<Lysosomal enzymes play a great role.>

When an epithelial cell is crushed, autolysis begins in the cell. As lysosomal enzymes are released into the cell, they begin to destroy their host cell. I think that after the host cell has been destroyed, the enzymes will not stop working.  

On the equator, epithelial cells are crushed by the PRESSURE, and in the deep cortex, fiber cells are injured by Pressure[b]1. In both crushed epithelial cells and injured fiber cells, lysosomal enzymes are released into the cells. After the enzymes decomposed the cell, the enzymes which have got out of the cell will attack another fiber cell and destroy it. Lysosomal enzymes continue to destroy the fiber cells. In this way, lysosomal enzymes play a great role, and advance the wedge-shaped cataract.

<How long do lysosomal enzymes work?>

It is said that a lysosome contains about 70 sorts of enzymes. Among those enzymes, the most important enzymes which will develop wedge-shaped cataract are proteases.

In a human lens, the capsule forms a closed environment like a cell. This is a closed space. (Fig.4-16) Edward Cotlier describes. “In the normal lens the membrane of the lens fibers and the lens capsule do not allow the passage of protein molecules from the lens to the aqueous humor.¹⁹”

Because lysosomal enzymes are proteins, they are not carried out of the lens, and in this enclosed special space, neither the blood stream nor the lymph flow exists. Therefore, the enzymes are not carried out of the space. The enzymes remain in the lens.

The half-life of these enzymes is known to be about 10 to 30 hours.²⁰ It is conceivable that after the enzymes have been released into the cell from the lysosomes, they might stay in the cell for about 10 to 30 hours before the enzymes get out of the host cell. If so, the enzymes cannot attack other cells.

Osato Miyawaki et al. wrote about the half-life of enzymes. Those enzymes were glucoamylase and β-galactosidase. “Half-life of enzyme increased by ten-to thousand-fold with coexistence of　substrate. ²¹” “Proteins are known to be marginally stable in an aqueous environment.²¹”

Substrate: A substance upon which an enzyme acts.¹

They said that the coexistence of substrate prolonged the half-life of enzymes to from 10 to 1,000 times. In a human lens, after lysosomal enzymes destroyed some epithelial cells, substances which the enzymes may attack remain plentifully. Therefore, there is the possibility that the life spans of those enzymes may drastically elongate and, if the catabolic enzymes are decomposed only by other catabolic enzymes, it is assumed that the life spans of those enzymes are prolonged further. In the lens, the probability that the enzymes meet one another is very small because of the plentiful substrates there. For this reason, the enzymes in the lens will hardly decompose. Accordingly, the life spans of enzymes will be extremely prolonged. It might be as much as 5 or 10 years.

Recurrent crush of the cells on the equator by the pressure and repeated attacks on the cells in the lens by the enzymes advance the destruction of the lens. As lysosomes in the fiber cell will continue decreasing depending on growth of the cell, it is assumed that new enzymes in the lens are supplied mainly from the collapse of epithelial cells.

In this way, the collapse of cells begins to occur all over the lens. Moreover, since other biochemical changes increase, the opaqueness of the cataract falls into great confusion.