Review: Age-related cataract: immunity and lens epithelium-derived growth factor (LEDGF)

Abstract

This short review summarizes our recent work and relevant publications on autoimmunity and cataract. A complete review of this subject is beyond the scope of this paper. Age-related cataract (ARC) is the leading cause of world blindness. In spite of more than fifty years of basic and clinical research, there is no nonsurgical intervention to prevent or treat ARC, but there is a better understanding of the manifold complexities of this age-related condition. ARC is a multifactorial condition in which incidence and progress are modified by factors such as age, sex, radiation [visible, ultraviolet (UV), and X-ray], oxidation, physical trauma, diet, and medications. The lens contains at least three different cell types: central epithelial cells, dividing germinative epithelial cells, and fiber cells. The central epithelial cells covering the anterior axial part of the lens do not divide but survive throughout life. The bulk of the lens comprises anucleate fiber cells, differentiated germinative epithelial cells, which have undergone an apoptosis-like change "diffoptosis" to become elongated, crystallin-rich, organelle-deficient, cells. The epithelial cells and their active transport mechanisms maintain lens homeostasis and clarity. The survival mechanisms of the central lens epithelial cells (LECs) are unknown. In other cells, growth or survival factors, when present, enhance survival and, when absent or deficient, induce programmed cell death "apoptosis". Many developing mammalian cells produce signal proteins, or require signal proteins from other cells, to avoid apoptosis. Although much is known about the role of growth factors in the lens, less is known about how such signals are involved in the survival and death of LECs. We have hypothesized that LECs, like other mammalian cells, use signal proteins to regulate growth, survival, and apoptosis, and we have begun a search for such molecules. Furthermore, we have hypothesized that such factors, if found, may also be involved in the death of LECs, the consequent alteration of lens homeostasis and, eventually, certain types of ARC.