The Role of IDO Activity in Cataract Progression: Correlation to Age and Cataract Severity

Purpose: Cataract is a prevalent, progressive lens disorder characterized by gradual opacity, often related to aging. Oxidative stress, ultraviolet radiation, and inflammation contribute to lens damage and protein modifications. Indoleamine 2,3-dioxygenase plays a critical role in tryptophan metabolism, with kynurenines implicated in various diseases. This study aimed to assess IDO activity in cataract patients by analyzing IDO activity in aqueous humor. Methods: The study included 170 cataract surgery patients (60 males, 110 females; mean age 73.9 ± 9.43 years). Cataract severity was categorized using the SPONCS system: SPONCS 1 (1.8%), SPONCS 2 (30.6%), SPONCS 3 (35.3%), SPONCS 4 (11.8%), and SPONCS 5 (20.6%). Aqueous humor samples (50–120 µL) were collected via paracentesis and analyzed using HILIC liquid chromatography with mass spectrometry. Target metabolite quantification was performed using internal standards and calibration curves. Results: Significant differences in IDO activity were observed across SPONCS groups (X²(4) = 12.0, p =.018, Ɛ²= 0.0707), particularly between SPONCS 2 and SPONCS 5 (p =.013). Age differences across SPONCS groups were also significant (p <.001). Males had lower tryptophan levels than females (p =.027). Correlations were found between SPONCS and IDO activity (r_s = −0.255, p <.001), SPONCS and kynurenine (r_s = 0.196, p =.011), and kynurenic acid with kynurenine (r_s = 0.355, p <.001). Conclusion: Patients with SPONCS 2 cataract exhibit increased susceptibility to elevated IDO activity and heightened kynurenine production. IDO serves as a more reliable prognostic marker for cataract progression than chronological age. Furthermore, IDO activity may be associated with reduced glutathione levels in human lens epithelial cells, suggesting a potential link between the enzyme and oxidative stress within the lens.