Purpose: Since the exact development of posterior subcapsular cataracts (PSCs) is poorly understood, we review various risk factors and propose a two-stage etiology for PSCs. Methods: The biological mechanisms associated with age-related cataracts (primarily nuclear cataracts, cortical cataracts and PSCs) were reviewed in relation to selected risk factors that induce PSCs (including atopy, diabetes, hypoparathyroidism, myopia, retinitis, solar radiation, steroid use, uveitis, vitrectomy and ionizing radiation). We particularly focused on ionizing radiation, as this is known to be a risk factor specific to PSCs. Based on an analysis of the reviewed material, we propose a detailed explanation of the etiology of PSCs. Conclusions: Lens epithelial cells (LECs) and lens fiber cells are normally hypoxic and therefore very sensitive to changes in oxidative stress, as quantified by the radiation oxygen effect. We hypothesize that the development of PSC opacities is a two-stage process. Stage I, early in life, is driven by risk factors that promote oxidative stress and ion-pump disruption, harming lens fibers and causing aberrant LECs to proliferate and ectopically migrate as Wedl cells (perhaps by processes associated with an epithelial to mesenchymal transition) to the posterior pole region. After a latent period, in Stage II, the development of PSCs advances mainly due to chronic inflammation and other premature aging-related mechanisms that promote mature vacuolar or plaque PSC. This two-stage hypothesis of PSC etiology accounts for risk factors, such as aging, diabetes and ionizing radiation, which directly affects LECs and the lens. In addition, these risk factors can damage other ocular regions, such as the retina and vitreous, that also indirectly contribute to the development of PSCs. It is possible that the incidence of PSCs may be reduced by reversing the effects of Stage I through various means, including ocular antioxidants.
Bibliographical noteFunding Information:
RBR undertook this work supported by the Atomic Energy of Canada Limited Federal Nuclear Science and Technology Plan. EAA received funding from LDLensRad, which is part of the CONCERT project. This project has also received funding from the Euratom research and training program 2014?2018 under grant agreement no. 662287. Dr. Douglas Borchman, University of Louisville, KY; Dr. Ying-Bo Shui of Washington University School of Medicine, St. Louis, MO; Dr. Judith West-Mays, McMaster University, Hamilton, ON; and Dr. Yi Wang, Dr. Megha Chandrashekhar and Dr. Fawaz Ali of CNL, Chalk River, ON are thanked for providing helpful comments on early drafts of this review. RBR has benefited from the library facilities that McGill University makes available to its adjunct professors. Carolyn Brown of Ottawa is thanked for her assistance in editing an early draft of the manuscript. RBR is the lead author and principal investigator. Coauthors EAA, CRP and FJL made substantial contributions to the paper.
- Posterior subcapsular cataract
- cataract etiology
- ionizing radiation
- oxidative stress