Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon?

Abstract

Cataracts, a leading cause of blindness worldwide, are closely linked to oxidative stress-induced damage to lens epithelial cells (LECs). Key factors contributing to cataract formation include aging, arterial hypertension, and diabetes mellitus. Given the high global prevalence of cataracts, the burden of cataract-related visual impairment is substantial, highlighting the need for pharmacological strategies to supplement surgical interventions. Understanding the molecular pathways involved in oxidative stress during cataract development may offer valuable insights for designing novel therapeutic approaches. This review explores the role of oxidative stress in cataract formation, focusing on critical mechanisms, such as mitochondrial dysfunction, endoplasmic reticulum stress, loss of gap junctions, and various cell death pathways in LECs. Additionally, we discuss emerging therapeutic strategies and potential targeting options, including antioxidant-based treatments.

Keywords: aging; antioxidants; cataract; diabetes; hypertension; novel treatment approaches; oxidative stress.

Figure 1

Schematic overview of the redox homeostasis in the lens, highlighting the role of endogenous antioxidants as well as of pro-oxidative, pro-inflammatory and pro-apoptotic agents, responsible for favoring processes of cataractogenesis. GSH: glutathione; GPx: glutathione peroxidase; NF-kB: nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells; NLRP3: NOD-like receptor protein 3; Prdx: peroxiredoxin; ROS: reactive oxygen species; Trx: thioredoxin.

Figure 2

Illustration of the central pathogenetic pathways during cataracto-genesis associated with aging, systemic hypertension or diabetes. ATP: adenosintriphosphat; Ca²⁺: calcium; ER: endoplasmic reticulum; GSH: glutathione; K⁺: potassium; mtDNA: mitochondrial DNA; Na⁺: sodium; NOX: nicotinamide adenine dinucleotide phosphate oxidase; ROS: reactive oxygen species; UPR: unfolded protein response. Upward arrows indicate upregulation or increased activity or increased concentration, whereas downward arrows indicate downregulation or decreased activity or decreased concentration.

Figure 3

Scheme of the molecular mechanisms of apoptosis, pyroptosis and ferroptosis, leading to LEC death during cataracto-genesis. Fe³⁺: ferric iron; •OH: hydroxyl radical; LEC: lens epithelial cell; NF-kB: nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells; NLRP3: NOD-like receptor protein 3. Upward arrows indicate upregulation or increased activity or increased concentration.

Figure 4

Representation of antioxidative effects, contrasting cataracto-genesis during aging, under hypertension and diabetes. GSH: glutathione; LEC: lens epithelial cell; Nrf2: nuclear factor-erythroid-2-related factor 2; RAAS: renin–angiotensin–aldosterone system.