A Personal View on Energy, Heat, and Entropy Dissipation in Corneal Tissue
The normal cornea maintains its transparency and serves as the outermost protective layer of the eye, shielding it from external stresses such as electromagnetic radiation, pathogens, and desiccation. Although it appears static and structurally ordered at the macroscopic level, the cornea is metabolically active at the microscopic level, as is typical for living tissue. Oxygen is absorbed from the external surface of the cornea, while nutrients are supplied via the aqueous humor of the anterior chamber. The metabolic activity of the cornea inevitably generates excretory byproducts, which are thought to dissipate both anteriorly and posteriorly. Anatomically, it is reasonable to consider that waste products are eliminated through the tear film on the epithelial surface and via the aqueous humor on the endothelial side.
Based on his lecture in Dublin, quantum physicist Erwin Schrödinger published What is Life?, in which he introduced the concept of entropy into the study of living systems and explored life from the standpoint of thermodynamics. He argued that living organisms maintain their internal order by importing "negative entropy" (or negentropy) to counterbalance the natural increase in entropy generated by their metabolic activities. (1) Although the concept of negative entropy remains a topic of scientific debate, the second law of thermodynamics—the tendency toward increasing entropy—is universally accepted, and living systems are not exempt from it. In this context, the excretion of waste products can be seen as a way to eliminate the entropy produced within the body, analogous to "eating negentropy" to preserve internal order.
The anatomy of the cornea consists of three main layers: the superficial corneal epithelium, the intermediate corneal stroma, and the innermost corneal endothelium. Between these layers lie two distinct membranes: Bowman's membrane, located between the epithelium and the stroma, and Descemet's membrane, situated between the stroma and the endothelium. The corneal epithelium is composed of multiple layers of stratified squamous cells that protect the ocular surface from mechanical, microbial, and environmental stresses. In contrast, the corneal endothelium consists of a single layer of hexagonally shaped cells, which are in direct contact with the aqueous humor of the anterior chamber. (Figure )
Life forms are commonly understood as non-equilibrium open systems, a concept famously discussed in Ilya Prigogine's theory of dissipative structures. (2)
According to this theory, when an object dissipates entropy thermodynamically, a characteristic structure emerges depending on the system's conditions. A well-known example of this is Bénard convection (Bénard cell), in which a fluid film, when heated uniformly from below, spontaneously forms hexagonal convection cells due to the dissipation of heat. These cells are strikingly similar in shape to the hexagonal structure of corneal endothelial cells found in the innermost layer of the cornea. The formation of such cells requires a Rayleigh number of 1710 or higher. In the corneal stroma, active energy metabolism is constantly at work, generating unwanted, high-entropy molecules. To maintain balance, a system is necessary to expel these molecules. Autophagy, an intracellular process that has been recently highlighted, is one potential pathway for entropy processing, although it primarily serves to handle inflow into the cell. For expelling entropy generated within the cornea, however, it is believed that the main outflow systems are tear fluid, blood flow, lymphatic flow, and the aqueous humor in the anterior chamber. Anatomically, the anterior chamber, which is in contact with the hexagonal endothelial cells formed by dissipative structures, is thought to be the primary pathway for the outflow of entropy.
In our speculation, there exists a horizontally stratified High Entropy Zone in the corneal stroma, located just below Bowman's layer, or on the epithelial side of the stroma. This zone, which is thought to have a high density of corneal stromal cells, would be expected to have relatively high temperature and entropy as a result of active cellular metabolism and biological activity. A temperature and entropy gradient is then expected to form within the corneal stroma. The generated entropy gradient is thought to be discharged towards the anterior chamber through the corneal endothelial cells, thus maintaining the cornea's transparency and its overall function.
(Figure )
In an experiment involving fluorescein dye injected into the corneal stroma, a horizontal swirling flow was observed (it suggests a spiral flow in the vertical direction), which was attributed to the function of the corneal endothelium. (3) Bénard convection is said to be accompanied by rotations and vortices, and convection caused by fluorescein dye may suggest this. Although there are some details that are unclear regarding the anatomical location of the outflow and inflow in the corneal endothelium and anterior chamber, assuming that the flow is similar to that of Bénard cell, the outflow probably flows out toward the anterior chamber from the central area of the corneal endothelium, while the inflow probably flows into the corneal stroma from the cell-cell junction.
If the overall outflow/inflow behavior results in entropic flow-induced spiral gyration forces in the corneal stroma and anterior chamber, then it is possible that a extremely slow rotating cell migration may be occurring in the corneal stroma and corneal endothelial cells. In addition to the generation of hexagonal cells by Bénard convection, it is also possible that a potential hexagonal flow of the aqueous humor may be also occurring in the anterior chamber space. An interesting recent report suggests that nano-dissipative structures also occur at the nanoscale, and entropy dissipation may occur at the nanoscale as well, forming nano-Bénard convection as well as classical dissipative structures. These processes of cell activity, metabolism, and entropy dissipation within the corneal stroma and endothelium might play significant roles in maintaining corneal transparency, regulating autoimmune responses (such as corneal autoantigen dynamics), supporting corneal transplant immunology, and enhancing the regeneration of corneal cells after injury or disease.
In conclusion, we expect that a laminar zone of high entropy is always spontaneously generated in the corneal stroma, and that Bénard convection occurs in the direction of the anterior chamber to dissipate the increased entropy, and that corneal stromal entropy is always ejected toward the anterior chamber together with the corneal endothelial entropy. The amount of entropy ejected from the endothelial surface (⊿S out) is never less than the amount of entropy generated in the stroma (⊿S in),
and we expect that ⊿S in - ⊿S out ≦ 0 may be always true. In the opposite case, due to the accumulation of excretory and waste molecules in the cornea and the equilibrium state of biological information, corneal stroma cells and corneal endothelial cells would lose their functionality, resulting in irreversible corneal damage and loss of transparency. Entropy dissipation from healthy corneal stromal cells promotes entropy dissipation from healthy corneal endothelial cells, which may also contribute to the maintenance of corneal endothelial function and the self-organization of corneal tissue. The above is entirely our personal view, but if true, we look forward to expanding this concept into the realm of quantum nano-entropy, where nanoscale dissipative structures and thermodynamic gradients might offer deeper insights into the quantum biological processes driving cellular behaviors and corneal regeneration.
References
1) Schrödinger, E: What is life ? The physical aspect of the living cell. Order, disorder and entropy. Reprint edition, Cambridge University Press,
Cambridge, 67-75, 1992
2) Prigogine, I: Time, structure and fluctuations. Science 201(4358):777-785, 1978
3) Inoue, T et al: Horizontal intracorneal swirling water migration indicative of corneal endothelial function. Invest Ophthalmol Vis Sci 55:8006-8014, 2014
May 07, 2025
Mejiro Dori Clinic (Ophthalmology)
Yasushi Sonoda, MD.
