Etiology of posterior subcapsular cataracts based on a review of risk factors including aging, diabetes, and ionizing radiation

Abstract

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.

Biliverdin/Bilirubin Redox Pair Protects Lens Epithelial Cells against Oxidative Stress in Age-Related Cataract by Regulating NF-κB/iNOS and Nrf2/HO-1 Pathways

“…For example, oxidative stress, especially GSH depletion, is regarded as the hallmark of ARNC [ 16 ]. Ionic imbalance caused by loss of Na + /K + -ATPase function and water content increase is the proposed mechanism for cortical cataract genesis, while ARPSC is more common in patients with retinitis pigmentosa, diabetes, myopia, and long-term use of corticosteroids [ 49 , 50 ]. Thus, it is no surprise that the relative mRNA expressions of Nrf2, HO-1, and BVRA, which are crucial for resisting oxidative stress, were all decreased in the LECs of ARNC patients.…”

Immune responses to injury and their links to eye disease

“…When untreated, uveitis can lead to scarring, swelling or detachment of the retina, optic nerve damage, glaucoma, and lens cataract, all of which are associated with vision loss. While this inflammatory disease has been linked to cataract formation [202], the exact mechanism is not yet known. In contrast, there is a significant literature showing post-cataract surgery complications in patients with uveitis, particularly if inflammation is not controlled prior to surgery.…”

Prior pars plana vitrectomy and its association with adverse intraoperative events during cataract surgery

“…Despite advances in surgical techniques, PPV frequently results in cataract, with some studies suggesting the rate of progression to visually significant nuclear sclerotic cataract is as high as 100% (Cheng et al 2001;Do et al 2018). Several hypotheses for this have been proposed including injury to the crystalline lens at the time of PPV, phototoxicity and lens protein oxidation (Hsuan et al 2001;Soliman et al 2018;Richardson et al 2020). Prior studies have suggested that while cataract surgery may improve visual acuity after PPV, it is associated with higher rates of intraoperative complications, including zonulopathy (such as zonular dehiscence or the need for a capsular tension ring), prolapsed lens fragments and posterior capsular tears (Grusha et al 1998;Pinter & Sugar 1999;Soliman et al 2018).…”

“…2018; Richardson et al. 2020). Prior studies have suggested that while cataract surgery may improve visual acuity after PPV, it is associated with higher rates of intraoperative complications, including zonulopathy (such as zonular dehiscence or the need for a capsular tension ring), prolapsed lens fragments and posterior capsular tears (Grusha et al.…”