Maintaining transparency: a review of the developmental physiology and pathophysiology of two avascular tissues

Abstract

The lens and cornea are transparent and usually avascular. Controlling nutrient supply while maintaining transparency is a physiological challenge for both tissues. During sleep and with contact lens wear the endothelial layer of the cornea may become hypoxic, compromising its ability to maintain corneal transparency. The mechanism responsible for establishing the avascular nature of the corneal stroma is unknown. In several pathological conditions, the stroma can be invaded by abnormal, leaky vessels, leading to opacification. Several molecules that are likely to help maintain the avascular nature of the corneal stroma have been identified, although their relative contributions remain to be demonstrated. The mammalian lens is surrounded by capillaries early in life. After the fetal vasculature regresses, the lens resides in a hypoxic environment. Hypoxia is likely to be required to maintain lens transparency. The vitreous body may help to maintain the low oxygen level around the lens. The hypothesis is presented that many aspects of the aging of the lens, including increased hardening, loss of accommodation (presbyopia), and opacification of the lens nucleus, are caused by exposure to oxygen. Testing this hypothesis may lead to prevention for nuclear cataract and insight into the mechanisms of lens aging. Although they are both transparent, corneal pathology is associated with an insufficient supply of oxygen, while lens pathology may involve excessive exposure to oxygen.

Figure 1

A. A diagram showing the hyaloid vasculature and the capillaries of the tunica vasculosa lentis and anterior pupillary membrane. B. Diagram showing the progressive loss of capillaries around the anterior (PM) and posterior (TVL) of the mouse lens in the first two weeks after birth. Figure modified from [2].

Figure 2

Proposed effects of oxygen on HIF-1 levels and function in young or old mice. In young or older animals, HIF-1 levels and activity are high, due to the hypoxic environment in the eye. Increasing oxygen exposure decreases HIF-1 levels in the lens. However, in young lenses, HIF-1 is not suppressing lens growth. Therefore, decreasing HIF-1 level and activity has no effect on BrdU incorporation, as shown in the graph to the right. In older animals, high HIF-1 levels suppress lens epithelial cell proliferation, as shown by low BrdU incorporation in the graph to the right. Raising intraocular oxygen decreases HIF-1 levels and HIF-1 transcriptional activity. This releases the inhibition of cell proliferation, permitting the growth factors that are normally present in the eye to stimulate lens epithelial cell proliferation, resulting in faster lens growth.

Figure 3

Examples of the common types of age related cataracts. The upper row of images shows Scheimpflug camera views of the normal lens and four types of age-related cataracts. The lower row of pictures are retroillumination images of the three common types of age-related cataracts (Photos courtesy of Dr. Ying-Bo Shui).