16 Apoptosis and Homeostasis in the Eye

Although the human eye is only a few centimeters in diameter, it contains an extraordinary array of cells and tissues, some of which are found in no other organ (Figure 16-1). The eye is an anatomical extension of the brain and processes an enormously complex array of information that provides us with our most precious sense – our vision. The retinal ganglion cells process more than 500 electrical signals per second, which is roughly equivalent to 109 bits of computer information. The conversion of photons of light that enter the eye to crisp visual images in the brain is orchestrated by a diverse array of cells and tissues with vastly different properties and functions. Apoptosis and apoptosislike processes contribute to the embryonic development of the mammalian eye in the womb and the long-term function of the visual axis from the time of birth to death. The eye, like other components of the central nervous system, is composed of cells that have limited and sometimes no capacity for regeneration. As a result, immune-mediated inflammation can lead to blindness. However, the fluids that fill the eye contain an extraordinary variety of immunosuppressive and antiinflammatory molecules that control inflammation produced by elements of the innate and adaptive immune systems. Among these eye-derived factors are molecules that induce apoptosis of inflammatory cells. In addition, antigens that enter the eye elicit a unique deviation of the immune response that actively suppresses antigenspecific immune responses such as delayed-type hypersensitivity (DTH), which nonspecifically damages innocent bystander cells within the eye. Interestingly, apoptosis is intimately involved in the induction of this ocular immune deviation.

1. APOPTOSIS AND APOPTOSIS-LIKE PROCESSES THAT

SHAPE THE DEVELOPMENT OF THE MAMMALIAN EYE

1.1. Lens

The lens of the mammalian eye grows throughout life, although the growth slows as we age. The lens is composed of two cell types that are derived from ectoderm: the lens epithelial cells and the lens fiber cells. The lens epithelial cells form the outermost layers of the lens and differentiate into lens fiber cells by an apoptosis-like process. Throughout life, the lens epithelial cells differentiate into lens fiber cells, which form the core of the lens. Thus the structure of the lens is somewhat like the layers of an onion, in which the outer layers are composed of the younger lens epithelial cells, and the inner layers are made up of the lens fiber cells that have undergone differentiation, which involves an apoptosis-like process. The differentiation of the lens begins with the elongation of the lens epithelial cells, which subsequently lose their organelles, including the nucleus, mitochondria, Golgi bodies, and endoplasmic reticulum. The nucleus of the lens epithelial cells becomes elongated, and eventually the nuclear membrane disappears and the nucleus itself is no longer distinguishable from the cytoplasmic contents. The denucleation process has many properties reminiscent of apoptosis and involves various regulators that are also involved in classical apoptosis, including members of the caspase family. Studies in the rat have shown that inhibitors of caspase-3-like enzymes block lens differentiation in vitro. Moreover, caspase- 3 transcripts are expressed in high amounts in developing lenses in rat eyes. Although various regulators of