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

This short review summarizes our recent work and relevant publications on a utoimmunity and cataract. A complete review of this subject is beyond the s cope of this paper. Age-related cataract (ARC) is the leading cause of world blindness (1). 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 und erstanding 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-ra y], oxidation, physical trauma, diet, and medications (2). The lens contains at least three different cell types: central epithelial c ells, dividing germinative epithelial cells, and fiber cells. The central e pithelial cells covering the anterior axial part of the lens do not divide but survive throughout life (3). The bulk of the lens comprises anucleate f iber cells, differentiated germinative epithelial cells, which have undergo ne an apoptosis-like change "diffoptosis" (4) to become elongated, crystall in-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 unk nown. In other cells, growth or survival factors, when present, enhance sur vival and, when absent or deficient, induce programmed cell death "apoptosi s"(5). Many developing mammalian cells produce signal proteins, or require signal proteins from other cells, to avoid apoptosis (6,7). Although much i s known about the role of growth factors in the lens, less is known about h ow such signals are involved in the survival and death of LECs. We have hyp othesized that LECs, like other mammalian cells, use signal proteins to reg ulate growth, survival, and apoptosis, and we have begun a search for such molecules. Furthermore, we have hypothesized that such factors, if found, m ay also be involved in the death of LECs, the consequent alteration of lens homeostasis and, eventually, certain types of ARC.