Impact of cellular and molecular organization on lens metabolism

The relationship between the metabolic gradient within the ocular lens and its cellular and molecular organization is discussed. The lens shares a number of organizational similarities with other stratified ectodermal tissues. All of these tissues were avascular and therefore, dependent upon the simple diffusion of nutrients from the surrounding medium. They contain non-metabolizing cell layers which are continually produced by an irreversible maturation process. This process is not random aging but a well orchestrated sequence of events dependent upon the physico-chemical properties of specialized proteins typical of each tissue. In the lens, these proteins are the crystallins. The signal for this maturation is decreased metabolism in conjunction with cell dehydration. Metabolism of these maturing cells is decreased by limited nutrient penetration because of barriers to nutrient diffusion and the high rate of utilization of nutrients by the more metabolically active cells near the basement membrane. Additionally, the regulation of anaerobic metabolism is dependent upon the maintenance and dissolution of an organized array of enzymes and the effects of dehydration, i.e. excluded volume effects and modified macromolecular organization. In the lens, the absence of metabolism during the maturation of the inner fiber cell layers is as important as the presence of active metabolism where differentiation and active protein synthesis occur. Therefore, any stress that disrupts tissue organization will have a detrimental effect on lens integrity.