{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:31:13Z","timestamp":1793043073764,"version":"4.5.0"},"reference-count":162,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Research Council of New Zealand"},{"name":"The Royal Society Marsden Fund"},{"name":"Auckland Medical Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress plays a major role in the formation of the cataract that is the result of advancing age, diabetes or which follows vitrectomy surgery. Glutathione (GSH) is the principal antioxidant in the lens, and so supplementation with GSH would seem like an intuitive strategy to counteract oxidative stress there. However, the delivery of glutathione to the lens is fraught with difficulties, including the limited bioavailability of GSH caused by its rapid degradation, anatomical barriers of the anterior eye that result in insufficient delivery of GSH to the lens, and intracellular barriers within the lens that limit delivery of GSH to its different regions. Hence, more attention should be focused on alternative methods by which to enhance GSH levels in the lens. In this review, we focus on the following three strategies, which utilize the natural molecular machinery of the lens to enhance GSH and\/or antioxidant potential in its different regions: the NRF2 pathway, which regulates the transcription of genes involved in GSH homeostasis; the use of lipid permeable cysteine-based analogues to increase the availability of cysteine for GSH synthesis; and the upregulation of the lens\u2019s internal microcirculation system, which is a circulating current of Na+ ions that drives water transport in the lens and with it the potential delivery of cysteine or GSH. The first two strategies have the potential to restore GSH levels in the epithelium and cortex, while the ability to harness the lens\u2019s internal microcirculation system offers the exciting potential to deliver and elevate antioxidant levels in its nucleus. This is an important distinction, as the damage phenotypes for age-related (nuclear) and diabetic (cortical) cataract indicate that antioxidant delivery must be targeted to different regions of the lens in order to alleviate oxidative stress. Given our increasing aging and diabetic populations it has become increasingly important to consider how the natural machinery of the lens can be utilized to restore GSH levels in its different regions and to afford protection from cataract.<\/jats:p>","DOI":"10.3390\/antiox13101193","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T03:57:52Z","timestamp":1727755072000},"page":"1193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Minimizing Oxidative Stress in the Lens: Alternative Measures for Elevating Glutathione in the Lens to Protect against Cataract"],"prefix":"10.3390","volume":"13","author":[{"given":"Julie C.","family":"Lim","sequence":"first","affiliation":[{"name":"Department Physiology, University of Auckland, Auckland 1023, New Zealand"},{"name":"Aotearoa New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5783-681X","authenticated-orcid":false,"given":"Lanpeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department Physiology, University of Auckland, Auckland 1023, New Zealand"},{"name":"Aotearoa New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha G.","family":"Lust","sequence":"additional","affiliation":[{"name":"Department Physiology, University of Auckland, Auckland 1023, New Zealand"},{"name":"Aotearoa New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4008-1138","authenticated-orcid":false,"given":"Paul J.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Department Physiology, University of Auckland, Auckland 1023, New Zealand"},{"name":"Aotearoa New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"key":"ref_1","first-page":"249","article-title":"Cataract blindness\u2014Challenges for the 21st century","volume":"79","author":"Brian","year":"2001","journal-title":"Bull. World Health Organ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1136\/bjophthalmol-2011-300539","article-title":"Global estimates of visual impairment: 2010","volume":"96","author":"Pascolini","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1001\/archopht.119.10.1439","article-title":"A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9","volume":"119","year":"2001","journal-title":"Arch. Ophthalmol."},{"key":"ref_4","first-page":"CD004567","article-title":"Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract","volume":"13","author":"Mathew","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"228","DOI":"10.4161\/oxim.3.4.12858","article-title":"Exogenous antioxidants--Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses","volume":"3","author":"Bouayed","year":"2010","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.5152\/eurasianjmed.2018.17397","article-title":"Reactive Oxygen Species: The Dual Role in Physiological and Pathological Conditions of the Human Body","volume":"50","author":"Bardaweel","year":"2018","journal-title":"Eurasian J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1245049","DOI":"10.1155\/2016\/1245049","article-title":"Role of ROS and RNS Sources in Physiological and Pathological Conditions","volume":"2016","author":"Reed","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1096\/fj.201700170R","article-title":"Physiological role of reactive oxygen species as promoters of natural defenses","volume":"31","author":"Roy","year":"2017","journal-title":"FASEB J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.exer.2004.02.004","article-title":"Platelet derived growth factor (PDGF)-induced reactive oxygen species in the lens epithelial cells: The redox signaling","volume":"78","author":"Chen","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3109\/10715762.2013.777155","article-title":"Antioxidants and cataract","volume":"47","author":"Thiagarajan","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Disease Study 2 Research, G. (2013). Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA, 309, 2005\u20132015.","DOI":"10.1001\/jama.2013.4997"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1167\/iovs.16-19162","article-title":"Expression Profiling of Ascorbic Acid\u2013Related Transporters in Human and Mouse Eyes","volume":"57","author":"Ma","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1203S","DOI":"10.1093\/ajcn\/54.6.1203s","article-title":"Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis","volume":"54","author":"Nishikimi","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1111\/ceo.13801","article-title":"Age-dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation\u2014A review","volume":"48","author":"Lim","year":"2020","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/jop.2000.16.121","article-title":"Glutathione: A vital lens antioxidant","volume":"16","author":"Giblin","year":"2000","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S1350-9462(03)00050-8","article-title":"Redox regulation in the lens","volume":"22","author":"Lou","year":"2003","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/0014-4835(90)90127-G","article-title":"Glutathione and its function in the lens\u2014An overview","volume":"50","author":"Reddy","year":"1990","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.exer.2004.12.007","article-title":"Age-related nuclear cataract-oxidation is the key","volume":"80","author":"Truscott","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.preteyeres.2016.09.002","article-title":"The physiological optics of the lens","volume":"56","author":"Donaldson","year":"2017","journal-title":"Progress Retin. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3109\/03008207.2013.867337","article-title":"Lens capsule as a model to study type IV collagen","volume":"55","author":"Cummings","year":"2014","journal-title":"Connect. Tissue Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1098\/rstb.2010.0302","article-title":"Biological glass: Structural determinants of eye lens transparency","volume":"366","author":"Bassnett","year":"2011","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_22","first-page":"174","article-title":"The content and structural characteristics of the collagenous protein of rabbit lens capsules at different ages","volume":"4","author":"Dische","year":"1965","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s002329900033","article-title":"Dye transfer between cells of the lens","volume":"150","author":"Rae","year":"1996","journal-title":"J. Membr. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1043-4682(10)80007-8","article-title":"The crystalline lens. A system networked by gap junctional intercellular communication","volume":"3","author":"Goodenough","year":"1992","journal-title":"Semin. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1083\/jcb.86.2.576","article-title":"Lens metabolic cooperation: A study of mouse lens transport and permeability visualized with freeze-substitution autoradiography and electron microscopy","volume":"86","author":"Goodenough","year":"1980","journal-title":"J. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.exer.2013.10.015","article-title":"Ultrastructural analysis of the human lens fiber cell remodeling zone and the initiation of cellular compaction","volume":"116","author":"Costello","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1152\/ajplegacy.1970.218.3.797","article-title":"Extracellular space of the crystalline lens","volume":"218","author":"Paterson","year":"1970","journal-title":"Am. J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1152\/physiologyonline.2001.16.3.118","article-title":"Molecular solutions to mammalian lens transparency","volume":"16","author":"Donaldson","year":"2001","journal-title":"Physiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1152\/physrev.1997.77.1.21","article-title":"Physiological properties of the normal lens","volume":"77","author":"Mathias","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00232-007-9019-y","article-title":"The lens circulation","volume":"216","author":"Mathias","year":"2007","journal-title":"J. Membr. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.exer.2017.06.012","article-title":"Comparison of the expression and spatial localization of glucose transporters in the rat, bovine and human lens","volume":"161","author":"Lim","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5142","DOI":"10.1167\/iovs.07-0649","article-title":"Mapping of glutathione and its precursor amino acids reveals a role for GLYT2 in glycine uptake in the lens core","volume":"48","author":"Lim","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.exer.2006.01.028","article-title":"Molecular identification and characterisation of the glycine transporter (GLYT1) and the glutamine\/glutamate transporter (ASCT2) in the rat lens","volume":"83","author":"Lim","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1167\/iovs.05-0156","article-title":"Molecular characterization of the cystine\/glutamate exchanger and the excitatory amino acid transporters in the rat lens","volume":"46","author":"Lim","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.exer.2013.09.002","article-title":"Molecular identification and cellular localization of a potential transport system involved in cystine\/cysteine uptake in human lenses","volume":"116","author":"Lim","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00418-019-01805-4","article-title":"Mapping of the cystine-glutamate exchanger in the mouse eye: A role for xCT in controlling extracellular redox balance","volume":"152","author":"Martis","year":"2019","journal-title":"Histochem. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101152","DOI":"10.1016\/j.preteyeres.2022.101152","article-title":"Regulation of lens water content: Effects on the physiological optics of the lens","volume":"95","author":"Donaldson","year":"2023","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.exer.2016.06.018","article-title":"Lens glutathione homeostasis: Discrepancies and gaps in knowledge standing in the way of novel therapeutic approaches","volume":"156","author":"Fan","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/0014-4835(85)90128-9","article-title":"Detoxification of H2O2 by cultured rabbit lens epithelial cells: Participation of the glutathione redox cycle","volume":"40","author":"Giblin","year":"1985","journal-title":"Exp. Eye Res."},{"key":"ref_40","unstructured":"Reddy, V.N., and Giblin, F.J. (1984). Ciba Found Symp, Wiley Online Library."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/02713680500477347","article-title":"Glutathione-related enzymes and the eye","volume":"31","author":"Ganea","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0014-4835(75)90060-3","article-title":"Total and oxidized glutathione in bovine corneal epithelium and endothelium","volume":"21","author":"Whikehart","year":"1975","journal-title":"Exp. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0014-5793(79)80069-1","article-title":"Hepatic mitochondrial and cytosolic glutathione content and the subcellular distribution of GSH-S-transferases","volume":"97","author":"Soboll","year":"1979","journal-title":"FEBS Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1001\/archopht.1957.00930050276018","article-title":"Studies on the glutathione in bovine lens","volume":"57","author":"Kinoshita","year":"1957","journal-title":"AMA Arch. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.exer.2017.10.010","article-title":"Functional characterisation of glutathione export from the rat lens","volume":"166","author":"Umapathy","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1167\/tvst.9.8.37","article-title":"Characterisation of Glutathione Export from Human Donor Lenses","volume":"9","author":"Li","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Minich, D.M., and Brown, B.I. (2019). A Review of Dietary (Phyto)Nutrients for Glutathione Support. Nutrients, 11.","DOI":"10.3390\/nu11092073"},{"key":"ref_48","first-page":"94","article-title":"Glutathione in the aqueous humor of human and other species","volume":"19","author":"Riley","year":"1980","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1167\/iovs.16-19592","article-title":"Evidence of dual mechanisms of glutathione uptake in the rodent lens: A novel role for vitreous humor in lens glutathione homeostasis","volume":"57","author":"Whitson","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1006\/exer.1996.0004","article-title":"Transport of circulating reduced glutathione at the basolateral side of the anterior lens epithelium: Physiologic importance and manipulations","volume":"62","author":"Mackic","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1006\/exer.1994.1134","article-title":"Blood-to-lens transport of reduced glutathione in an in situ perfused guinea-pig eye","volume":"59","author":"Zlokovic","year":"1994","journal-title":"Exp. Eye Res."},{"key":"ref_52","first-page":"37","article-title":"Modelling cortical cataractogenesis XXIV: Uptake by the lens of glutathione injected into the rat","volume":"5","author":"Dzialoszynski","year":"1999","journal-title":"Mol. Vis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.exer.2004.06.029","article-title":"The presence of a transsulfuration pathway in the lens: A new oxidative stress defense system","volume":"79","author":"Persa","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Fan, X., Liu, X., Hao, S., Wang, B., Robinson, M.L., and Monnier, V.M. (2012). The LEGSKO mouse: A mouse model of age-related nuclear cataract based on genetic suppression of lens glutathione synthesis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050832"},{"key":"ref_55","first-page":"381","article-title":"Glutathione and lens epithelial function","volume":"15","author":"Giblin","year":"1976","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S0014-4835(71)80043-X","article-title":"Metabolism of glutathione in the lens","volume":"11","author":"Reddy","year":"1971","journal-title":"Exp. Eye Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1006\/exer.1994.1084","article-title":"Ageing of glutathione reductase in the lens","volume":"59","author":"Zhang","year":"1994","journal-title":"Exp. Eye Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.exer.2008.08.001","article-title":"Synergistic effect of osmotic and oxidative stress in slow-developing cataract formation","volume":"87","author":"Chan","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ajo.2004.09.046","article-title":"Vitrectomy surgery increases oxygen exposure to the lens: A possible mechanism for nuclear cataract formation","volume":"139","author":"Holekamp","year":"2005","journal-title":"Am. J. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1001\/archophthalmol.2008.621","article-title":"The gel state of the vitreous and ascorbate-dependent oxygen consumption: Relationship to the etiology of nuclear cataracts","volume":"127","author":"Shui","year":"2009","journal-title":"Arch. Opthalmol."},{"key":"ref_61","first-page":"174","article-title":"Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) method: III. The association of nuclear color (sclerosis) with extent of cataract formation, age, and visual acuity","volume":"25","author":"Chylack","year":"1984","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0014-4835(80)80044-3","article-title":"Sulfur oxidation in selected human cortical cataracts and nuclear cataracts","volume":"31","author":"Garner","year":"1980","journal-title":"Exp. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1073\/pnas.77.3.1274","article-title":"Selective oxidation of cysteine and methionine in normal and senile cataractous lenses","volume":"77","author":"Garner","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0014-4835(77)90126-9","article-title":"The state of sulphydryl groups in normal and cataractous human lenses","volume":"25","author":"Truscott","year":"1977","journal-title":"Exp. Eye Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1073\/pnas.75.7.3244","article-title":"Disulfide-linked high molecular weight protein associated with human cataract","volume":"75","author":"Spector","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/ICU.0000000000001009","article-title":"Oxidative stress and antioxidants in cataract development","volume":"35","author":"Lee","year":"2024","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"32694","DOI":"10.1074\/jbc.M114.597898","article-title":"Connexin 46 (cx46) gap junctions provide a pathway for the delivery of glutathione to the lens nucleus","volume":"289","author":"Slavi","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1167\/iovs.13-12593","article-title":"The effects of age on lens transport","volume":"54","author":"Gao","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000055612","article-title":"Age-related nuclear cataract: A lens transport problem","volume":"32","author":"Truscott","year":"2000","journal-title":"Ophthalmic Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.2337\/dc10-S062","article-title":"Diagnosis and classification of diabetes mellitus","volume":"33","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1007\/s00125-010-1746-4","article-title":"Evidence that BMI and type 2 diabetes share only a minor fraction of genetic variance: A follow-up study of 23,585 monozygotic and dizygotic twins from the Finnish Twin Cohort Study","volume":"53","author":"Lehtovirta","year":"2010","journal-title":"Diabetologia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/oxfordjournals.aje.a010235","article-title":"Risk factors for cortical, nuclear, and posterior subcapsular cataracts: The POLA study. Pathologies Oculaires Liees a l\u2019Age","volume":"151","author":"Delcourt","year":"2000","journal-title":"Am. J. Epidemiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/eye.1993.60","article-title":"The lens in diabetes","volume":"7","author":"Bron","year":"1993","journal-title":"Eye"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0002-9394(14)71170-5","article-title":"Incidence of cataract surgery in the Wisconsin Epidemiologic Study of Diabetic Retinopathy","volume":"119","author":"Klein","year":"1995","journal-title":"Am. J. Ophthalmol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/09286589509071451","article-title":"Older-onset diabetes and lens opacities. The Beaver Dam Eye Study","volume":"2","author":"Klein","year":"1995","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0009-9120(01)00284-3","article-title":"Lens superoxide dismutase and catalase activities in diabetic cataract","volume":"35","author":"Ozmen","year":"2002","journal-title":"Clin. Biochem."},{"key":"ref_77","first-page":"173","article-title":"Human diabetic cataract: Role of lipid peroxidation","volume":"21","author":"Altomare","year":"1995","journal-title":"Diabete Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1076\/ceyr.25.1.9.9960","article-title":"Blood and lens lipid peroxidation and antioxidant status in normal individuals, senile and diabetic cataractous patients","volume":"25","author":"Donma","year":"2002","journal-title":"Curr. Eye Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1177\/000456329703400211","article-title":"Lens lipid peroxides and glutathione concentrations in diabetic cataract","volume":"34","author":"Ozmen","year":"1997","journal-title":"Ann. Clin. Biochem."},{"key":"ref_80","first-page":"357","article-title":"Studies on protein and taurine in normal, senile and diabetic cataractous human lenses","volume":"48","author":"Anthrayose","year":"2004","journal-title":"Indian J. Physiol. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.exer.2017.05.014","article-title":"Does oxidative stress play any role in diabetic cataract formation?\u2014Re-evaluation using a thioltransferase gene knockout mouse model","volume":"161","author":"Zhang","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_82","first-page":"800","article-title":"Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency","volume":"16","author":"Chee","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.exer.2017.08.009","article-title":"The modulation of the phosphorylation status of NKCC1 in organ cultured bovine lenses: Implications for the regulation of fiber cell and overall lens volume","volume":"165","author":"Vorontsova","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1167\/iovs.14-15911","article-title":"Identification of the WNK-SPAK\/OSR1 signaling pathway in rodent and human lenses","volume":"56","author":"Vorontsova","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0002-9394(01)01263-6","article-title":"Duration of vitrectomy and postoperative cataract in the vitrectomy for macular hole study","volume":"132","author":"Cheng","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0002-9394(14)72377-3","article-title":"Nuclear sclerotic cataract after vitrectomy for idiopathic epiretinal membranes causing macular pucker","volume":"111","author":"Cherfan","year":"1991","journal-title":"Am. J. Ophthalmol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.2147\/OPTH.S68661","article-title":"Cataract formation following vitreoretinal procedures","volume":"8","author":"Feng","year":"2014","journal-title":"Clin. Ophthalmol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/s41433-022-02181-5","article-title":"Ophthalmic surgery in New Zealand: Analysis of 410,099 surgical procedures and nationwide surgical intervention rates from 2009 to 2018","volume":"37","author":"Hossain","year":"2023","journal-title":"Eye"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.1167\/iovs.10-5666","article-title":"Oxygen distribution in the human eye: Relevance to the etiology of open-angle glaucoma after vitrectomy","volume":"51","author":"Siegfried","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/IIO.0000000000000440","article-title":"The Postvitrectomy Cataract","volume":"62","author":"Markatia","year":"2022","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/02713683.2020.1809002","article-title":"Glutathione Improves the Antioxidant Activity of Vitamin C in Human Lens and Retinal Epithelial Cells: Implications for Vitreous Substitutes","volume":"46","author":"Tram","year":"2021","journal-title":"Curr. Eye Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/BF02284971","article-title":"The systemic availability of oral glutathione","volume":"43","author":"Witschi","year":"1992","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1089\/acm.2010.0716","article-title":"Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers","volume":"17","author":"Allen","year":"2011","journal-title":"J. Altern. Complement. Med."},{"key":"ref_94","first-page":"121","article-title":"Topical glutathione therapy in senile cataracts. Cataract-III","volume":"37","author":"Sharma","year":"1989","journal-title":"Indian. J. Ophthalmol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Maddirala, Y., Tobwala, S., Karacal, H., and Ercal, N. (2017). Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats. BMC Ophthalmol., 17.","DOI":"10.1186\/s12886-017-0443-1"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"109610","DOI":"10.1016\/j.exer.2023.109610","article-title":"N-Acetylcysteine amide (NACA) and diNACA inhibit H2O2-induced cataract formation ex vivo in pig and rat lenses","volume":"234","author":"Martis","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Williams, R., Cauldbeck, H., and Kearns, V. (2024). Sustained-release drug delivery systems. Eye.","DOI":"10.1038\/s41433-024-03134-w"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1208\/s12249-023-02516-9","article-title":"Ocular Drug Delivery: A Comprehensive Review","volume":"24","author":"Ahmed","year":"2023","journal-title":"AAPS PharmSciTech"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2015.06.021","article-title":"Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease","volume":"88","author":"Tebay","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Vomund, S., Schafer, A., Parnham, M.J., Brune, B., and von Knethen, A. (2017). Nrf2, the Master Regulator of Anti-Oxidative Responses. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122772"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Jaganjac, M., Milkovic, L., Sunjic, S.B., and Zarkovic, N. (2020). The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies. Antioxidants, 9.","DOI":"10.3390\/antiox9111151"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.freeradbiomed.2009.07.035","article-title":"Nrf2:INrf2 (Keap1) signaling in oxidative stress","volume":"47","author":"Kaspar","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/bdd.680","article-title":"Nrf2 plays an important role in coordinated regulation of Phase II drug metabolism enzymes and Phase III drug transporters","volume":"30","author":"Shen","year":"2009","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"11632","DOI":"10.1016\/S0021-9258(18)99004-6","article-title":"The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity","volume":"266","author":"Rushmore","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Bejarano, E., Weinberg, J., Clark, M., Taylor, A., Rowan, S., and Whitcomb, E.A. (2023). Redox Regulation in Age-Related Cataracts: Roles for Glutathione, Vitamin C, and the NRF2 Signaling Pathway. Nutrients, 15.","DOI":"10.3390\/nu15153375"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.freeradbiomed.2008.10.040","article-title":"Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress","volume":"46","author":"Harvey","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e00099-20","DOI":"10.1128\/MCB.00099-20","article-title":"The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11908","DOI":"10.1073\/pnas.172398899","article-title":"Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants","volume":"99","author":"Holtzclaw","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1101\/gad.13.1.76","article-title":"Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain","volume":"13","author":"Itoh","year":"1999","journal-title":"Genes Dev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1128\/MCB.26.1.221-229.2006","article-title":"Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1","volume":"26","author":"Kobayashi","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1073\/pnas.0307301101","article-title":"Protection against electrophile and oxidant stress by induction of the phase 2 response: Fate of cysteines of the Keap1 sensor modified by inducers","volume":"101","author":"Wakabayashi","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"8137","DOI":"10.1128\/MCB.23.22.8137-8151.2003","article-title":"Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress","volume":"23","author":"Zhang","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.mam.2008.08.009","article-title":"Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase","volume":"30","author":"Franklin","year":"2009","journal-title":"Mol. Asp. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/carcin\/bgaa039","article-title":"NRF2 as a regulator of cell metabolism and inflammation in cancer","volume":"41","author":"He","year":"2020","journal-title":"Carcinogenesis"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim. Biophys. Acta-Gen. Subj."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/iovs.62.15.10","article-title":"Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts","volume":"62","author":"Rowan","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Oh, Y.S., and Jun, H.S. (2017). Effects of Glucagon-Like Peptide-1 on Oxidative Stress and Nrf2 Signaling. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010026"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1006\/exer.1996.0002","article-title":"Effect of selected anti-cataract agents on opacification in the selenite cataract model","volume":"62","author":"Hiraoka","year":"1996","journal-title":"Exp. Eye Res."},{"key":"ref_120","first-page":"2550","article-title":"Inhibition of lens opacification during the early stages of cataract formation","volume":"36","author":"Hiraoka","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2478\/v10102-010-0005-3","article-title":"Different experimental approaches in modelling cataractogenesis: An overview of selenite-induced nuclear cataract in rats","volume":"3","author":"Kyselova","year":"2010","journal-title":"Interdiscip. Toxicol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1006\/exer.1996.0220","article-title":"Loss of cytoskeletal proteins and lens cell opacification in the selenite cataract model","volume":"64","author":"Matsushima","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_123","first-page":"8","article-title":"Selenite nuclear cataract: Review of the model","volume":"3","author":"Shearer","year":"1997","journal-title":"Mol. Vis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1385\/BTER:75:1-3:129","article-title":"Disulfonic stilbene prevents selenite-induced cataract in rat pup lens","volume":"75","author":"Yilmaz","year":"2000","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.bbadis.2014.06.028","article-title":"Selenite cataracts: Activation of endoplasmic reticulum stress and loss of Nrf2\/Keap1-dependent stress protection","volume":"1842","author":"Palsamy","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1080\/02713683.2019.1633359","article-title":"Protective Effects of Trimetazidine in Retarding Selenite-Induced Lens Opacification","volume":"44","author":"Fang","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"687","DOI":"10.18240\/ijo.2023.05.03","article-title":"Protective effects of ferulic acid against ionizing radiation-induced oxidative damage in rat lens through activating Nrf2 signal pathway","volume":"16","author":"Chen","year":"2023","journal-title":"Int. J. Ophthalmol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"5236","DOI":"10.1167\/iovs.13-11664","article-title":"Sulforaphane can protect lens cells against oxidative stress: Implications for cataract prevention","volume":"54","author":"Liu","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Chhunchha, B., Kubo, E., Krueger, R.R., and Singh, D.P. (2023). Hydralazine Revives Cellular and Ocular Lens Health-Span by Ameliorating the Aging and Oxidative-Dependent Loss of the Nrf2-Activated Cellular Stress Response. Antioxidants, 12.","DOI":"10.3390\/antiox12010140"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.3892\/mmr.2014.2849","article-title":"Human age-related cataracts: Epigenetic suppression of the nuclear factor erythroid 2-related factor 2-mediated antioxidant system","volume":"11","author":"Gao","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.bbrc.2012.05.164","article-title":"Promoter demethylation of Keap1 gene in human diabetic cataractous lenses","volume":"423","author":"Palsamy","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.diabres.2018.06.020","article-title":"LncRNA MALAT1 promotes the apoptosis and oxidative stress of human lens epithelial cells via p38MAPK pathway in diabetic cataract","volume":"144","author":"Gong","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.exer.2014.01.021","article-title":"Valproic acid suppresses Nrf2\/Keap1 dependent antioxidant protection through induction of endoplasmic reticulum stress and Keap1 promoter DNA demethylation in human lens epithelial cells","volume":"121","author":"Palsamy","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/j.1745-7254.2008.00837.x","article-title":"Ginkgo biloba extract prevents against apoptosis induced by high glucose in human lens epithelial cells","volume":"29","author":"Wu","year":"2008","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.3892\/mmr.2015.3490","article-title":"Acetyl-l-carnitine prevents homocysteine-induced suppression of Nrf2\/Keap1 mediated antioxidation in human lens epithelial cells","volume":"12","author":"Yang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Chhunchha, B., Kubo, E., and Singh, D.P. (2019). Sulforaphane-Induced Klf9\/Prdx6 Axis Acts as a Molecular Switch to Control Redox Signaling and Determines Fate of Cells. Cells, 8.","DOI":"10.3390\/cells8101159"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Kubo, E., Chhunchha, B., Singh, P., Sasaki, H., and Singh, D.P. (2017). Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2\/ARE\/Prdx6 activity during aging and oxidative stress. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-14520-8"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0006-3495(92)81624-7","article-title":"Spatial variations in membrane properties in the intact rat lens","volume":"63","author":"Baldo","year":"1992","journal-title":"Biophys. J."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1006\/exer.1996.0260","article-title":"Low de novo glutathione synthesis from circulating sulfur amino acids in the lens epithelium","volume":"64","author":"Mackic","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"37423","DOI":"10.1074\/jbc.M506439200","article-title":"Redox imbalance in cystine\/glutamate transporter-deficient mice","volume":"280","author":"Sato","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00204-021-03211-z","article-title":"Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for acetaminophen overdose","volume":"96","author":"Akakpo","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3109\/10715762.2013.781595","article-title":"N-Acetylcysteine amide: A derivative to fulfill the promises of N-Acetylcysteine","volume":"47","author":"Sunitha","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref_143","first-page":"862","article-title":"Effects of N-acetylcysteine and glutathione ethyl ester drops on streptozotocin-induced diabetic cataract in rats","volume":"14","author":"Zhang","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1080\/02713680802676885","article-title":"Prevention of selenite-induced cataractogenesis by N-acetylcysteine in rats","volume":"34","author":"Aydin","year":"2009","journal-title":"Curr. Eye Res."},{"key":"ref_145","first-page":"2221","article-title":"Topical application of L-arginine blocks advanced glycation by ascorbic acid in the lens of hSVCT2 transgenic mice","volume":"17","author":"Fan","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_146","first-page":"2945","article-title":"Hyperoxia-induced lens damage in rabbit: Protective effects of N-acetylcysteine","volume":"15","author":"Wang","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.lfs.2008.03.016","article-title":"Effects of N-acetylcysteine amide (NACA), a thiol antioxidant on radiation-induced cytotoxicity in Chinese hamster ovary cells","volume":"82","author":"Wu","year":"2008","journal-title":"Life Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3109\/10715762.2013.819974","article-title":"N-acetylcysteine amide, a thiol antioxidant, prevents bleomycin-induced toxicity in human alveolar basal epithelial cells (A549)","volume":"47","author":"Tobwala","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1177\/1535370214549520","article-title":"Comparative evaluation of N-acetylcysteine and N-acetylcysteineamide in acetaminophen-induced hepatotoxicity in human hepatoma HepaRG cells","volume":"240","author":"Tobwala","year":"2015","journal-title":"Exp. Biol. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.freeradbiomed.2010.12.017","article-title":"In vivo inhibition of l-buthionine-(S,R)-sulfoximine-induced cataracts by a novel antioxidant, N-acetylcysteine amide","volume":"50","author":"Carey","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_151","unstructured":"Wall, G.M., Johnson, D., Rubenstein, A., Tucker, R., and Bolger, J. (2020). Method for Preparation of N-Acetyl Cysteine Amide and Derivatives. (No. 10,590,073), U.S. Patent."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s13023-022-02367-w","article-title":"Evaluation of NACA and diNACA in human cystinosis fibroblast cell cultures as potential treatments for cystinosis","volume":"17","author":"Hector","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1089\/jop.2000.16.137","article-title":"Thiol regulation in the lens","volume":"16","author":"Lou","year":"2000","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"R994","DOI":"10.1152\/ajpregu.00180.2018","article-title":"The lens internal microcirculation system delivers solutes to the lens core faster than would be predicted by passive diffusion","volume":"315","author":"Vaghefi","year":"2018","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Zahraei, A., Guo, G., Varnava, K.G., Demarais, N.J., Donaldson, P.J., and Grey, A.C. (2022). Mapping Glucose Uptake, Transport and Metabolism in the Bovine Lens Cortex. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.901407"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1085\/jgp.201010538","article-title":"Lens intracellular hydrostatic pressure is generated by the circulation of sodium and modulated by gap junction coupling","volume":"137","author":"Gao","year":"2011","journal-title":"J. Gen. Physiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/j.bpj.2015.09.018","article-title":"Feedback Regulation of Intracellular Hydrostatic Pressure in Surface Cells of the Lens","volume":"109","author":"Gao","year":"2015","journal-title":"Biophys. J."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"C1751","DOI":"10.1152\/ajpcell.00010.2012","article-title":"TRPV4 in porcine lens epithelium regulates hemichannel-mediated ATP release and Na-K-ATPase activity","volume":"302","author":"Shahidullah","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1167\/iovs.61.6.58","article-title":"Signaling between TRPV1\/TRPV4 and Intracellular Hydrostatic Pressure in the Mouse Lens","volume":"61","author":"Delamere","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"C969","DOI":"10.1152\/ajpcell.00391.2019","article-title":"TRPV1 activation stimulates NKCC1 and increases hydrostatic pressure in the mouse lens","volume":"318","author":"Shahidullah","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"4416","DOI":"10.1167\/iovs.19-27794","article-title":"The Ciliary Muscle and Zonules of Zinn Modulate Lens Intracellular Hydrostatic Pressure through Transient Receptor Potential Vanilloid Channels","volume":"60","author":"Chen","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Petrova, R.S., Nair, N., Bavana, N., Chen, Y., Schey, K.L., and Donaldson, P.J. (2023). Modulation of Membrane Trafficking of AQP5 in the Lens in Response to Changes in Zonular Tension Is Mediated by the Mechanosensitive Channel TRPV1. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24109080"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/10\/1193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:08:31Z","timestamp":1760112511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/10\/1193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,1]]},"references-count":162,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["antiox13101193"],"URL":"https:\/\/doi.org\/10.3390\/antiox13101193","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,1]]}}}