Normal lens

Abstract: The lens is an avascular organ suspended between the aqueous and vitreous humors of the eye. The cellular structure is symmetric about an axis passing through its anterior and posterior poles but asymmetric about a plane passing through its equator. Because of its asymmetric structure, the lens has historically been assumed to perform transport between the aqueous and vitreous humors. Indeed, when anterior and posterior surfaces were isolated in an Ussing chamber, a translens current was measured. However, in the eye, the two surfaces are not isolated. The vibrating probe technique showed the current densities at the surface of a free-standing lens were surprisingly large, about an order of magnitude greater than measured in an Ussing chamber, and were not directed across the lens. Rather, they were inward in the region of either anterior or posterior pole and outward at the equator. This circulating current is the most dramatic physiological property of a normal lens. We believe it is essential to maintain clarity; hence, this review focuses on factors likely to drive and direct it. We review properties and spatial distribution of lens Na+/K+ pumps, ion channels, and gap junctions. Based on these data, we propose a model in which the difference in electromotive potential of surface versus interior cell membranes drives the current, whereas the distribution of gap junctions directs the current in the observed pattern. Although this model is clearly too simple, it appears to quantitatively predict observed currents. However, the model also predicts fluid will move in the same pattern as ionic current. We therefore speculate that the physiological role of the current is to create an internal circulatory system for the avascular lens.

Abstract: Our laboratory undertook extensive light, transmission (TEM) and scanning elctron microscope (SEM) studies of rat lenses during the development and reversal phase of galactose-induced cataracts. These studies were undertaken in order to gain insight into the morphological manifestation of known biochemical changes that accompany development and reversal of galactose cataracts. In a recent report we presented TEM studies describing ultrastructural alterations associated with induction and reversal of galactose cataracts in rat lens. This report presents SEM findings of lenses undergoing such processes. Lenses of galactose and Purina Lab Chow-fed 50 g Sprague-Dawley rats were removed at desired times after initiation of diet and processed for SEM. When examined with SEM, some of the alterations induced with galactose included intercellular cyst formation, decrease in inter-digitations between fibers, abnormal configurations, conformation, granulation roughening and fragmentation of the lens fibers. These alterations progressed from equatorial regions to lens nucleus. Upon removal of galactose from the diet after the establishment of mature cataracts, normal lens fiber morphology was reestablished and the progression of normalization followed similar equator to nucleus pattern. However, lens damage and transparency was not restored throughout the lens even after 90 days following cessation of galactose when small nuclear opacity and damage was still evident. These observations compliment TEM findings reported previously from our laboratory. A probable mechanism for the reestablishment of lens transparency is proposed.

Abstract: The mammalian lens generates an internal microcirculation that maintains transparency in the avascular lens. Significant progress has been made in characterizing the membrane transport proteins associated with this circulation. By combining physiological and molecular evidence, a more comprehensive understanding of normal lens function and cataractogenesis is emerging.

Abstract: To investigate the role of the intermediate filament protein vimentin in the normal differentiation and morphogenesis of the eye lens fiber cells, we generated transgenic mice bearing multiple copies of the chicken vimentin gene. In most cases, the vimentin transgene was overexpressed in the lenses of these animals, reaching up to 10 times the endogenous levels. This high expression of vimentin interfered very strongly with the normal differentiation of the lens fibers. The normal fiber cell denucleation and elongation processes were impaired and the animals developed pronounced cataracts, followed by extensive lens degeneration. The age of appearance and extent of these abnormalities in the different transgenic lines were directly related to the vimentin level. Electron microscopic analysis revealed that the accumulated transgenic protein forms normal intermediate filaments.