sodium-iodate and Cataract

Cataract and geographic atrophy (GA, also called advanced "dry" age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies.. We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84-7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR=3.23, 95% CI: 0.63-16.47). Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO(3) in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice.. Therefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.

Topics: alpha-Crystallin A Chain; Animals; Blotting, Western; Cataract; Cataract Extraction; Cells, Cultured; Electroretinography; Geographic Atrophy; Humans; Immunohistochemistry; Iodates; Mice; Mice, Knockout; Oxidative Stress; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction

Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in age-related cataract (ARC) with severe visual impairment, in which ferroptosis is gradually receiving numerous attention resulting from lipid peroxide accumulation and reactive oxygen species (ROS) overproduction. However, the essential pathogenic factors and the targeted medical strategies still remain skeptical and indistinct. In this work, by transmission electron microscopy (TEM) analysis, the major pathological courses in the LECs of ARC patients have been identified as ferroptosis, which was manifested with remarkable mitochondrial alterations, and similar results were found in aged mice (24-month-old). Furthermore, the primary pathological processes in the NaIO3-induced mice and HLE-B3 cell model have also been verified to be ferroptosis with an irreplaceable function of Nrf2, proved by the increased sensitivity to ferroptosis when Nrf2 was blocked in Nrf2-KO mice and si-Nrf2-treated HLE-B3 cells. Importantly, it has been found that an increased expression of GSK-3β was indicated in low-Nrf2-expressed tissues and cells. Subsequently, the contributions of abnormal GSK-3β expression to NaIO3-induced mice and HLE-B3 cell model were further evaluated, inhibition of GSK-3β utilizing SB216763 significantly alleviated LECs ferroptosis with less iron accumulation and ROS generation, as well as reversed expression alterations of ferroptosis markers, including GPX4, SLC7A11, SLC40A1, FTH1 and TfR1, in vitro and in vivo. Collectively, our findings conclude that targeting GSK-3β/Nrf2 balance might be a promising therapeutic strategy to mitigate LECs ferroptosis and thus probably delay the pathogenesis and development of ARC.

Topics: Animals; Antioxidants; Cataract; Epithelial Cells; Ferroptosis; Glycogen Synthase Kinase 3 beta; Mice; NF-E2-Related Factor 2; Reactive Oxygen Species

The effect of sodium iodate injection on the development of galactose cataract in the rat was investigated clinically and biochemically. Galactose cataracts were induced in animals which had been injected with a single dose of sodium iodate and compared with those given a saline injection. The degeneration of retinal pigment epithelium was observed electron microscopically after sodium iodate injection. A slit lamp examination of the lens showed that, in animals injected with sodium iodate, galactose-associated lens alterations progressed faster, and mature cataract development was achieved earlier than in the saline-injected animals. Biochemical data which indicated a significantly higher concentration of Na+ and lower concentration of K+ in lenses of sodium iodate-injected animals confirmed the above clinical data. The level of galactitol was higher in lenses of sodium iodate-injected than those of saline-injected animals. Acceleration of the development of galactose cataract following sodium iodate injection is apparently due to the higher level of galactose entering the aqueous humor because of breakdown of blood-ocular barriers.

Topics: Animals; Cataract; Diet; Female; Galactitol; Galactose; Injections; Iodates; Iodine; Lens, Crystalline; Male; Microscopy, Electron; Potassium; Rats; Rats, Inbred Strains; Retina; Sodium