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. Keywords hypoxia; neovascularization; cataract; avascular; oxygen Developmental PhysiologyThe lens and cornea have physiological similarities and structural differences. In spite of their different anatomical features, for both tissues to maintain transparency, their cells must obtain needed metabolites and be protected from harmful influences from the environment. The manner in which the lens and cornea manage these physiological challenges and the impact of these solutions on their function and pathology are the topic of this review.A dominant feature of the physiology of the lens and cornea of most mammals is their avascular nature in adult life. The cornea is avascular at all stages of its development. In mammals, the fetal lens is invested with a network of capillaries that regresses late in fetal or early postnatal life.

Oxidative Damage and the Prevention of Age-Related Cataracts

“…Several lines of evidence have led to the suggestion that exposure to elevated levels of molecular oxygen can cause nuclear cataracts [56][57][58][59] . However, under normal conditions, the level of oxygen around the human lens is very low, protecting the lens from this potential source of damage [58,60] .…”

Polymorphic Fibrillation of the Destabilized Fourth Fasciclin-1 Domain Mutant A546T of the Transforming Growth Factor-β-induced Protein (TGFBIp) Occurs through Multiple Pathways with Different Oligomeric Intermediates

“…However, no deposits of TGFBIp aggregates have been observed elsewhere in the human body. This has been suggested to be linked to the slow turnover of proteins in the cornea due to a lack of blood vessels (22). Furthermore, a C-terminal fragment of TGFBIp derived from FAS1-4 has been found to accumulate in amyloids of the mutant V624M, forming lattice-type deposits in the cornea (23).…”

Emerging techniques to treat corneal neovascularisation

“…These include cartilage, heart valves, and in the eye cornea, vitreous and lens. [15][16][17][18] In these tissues, mechanisms are in place to inhibit ingrowth of blood vessels. To maintain what has been termed the 'angiogenic privilege' in the cornea, a delicate balance exists between pro-and antiangiogenic factors (Figure 2).…”