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

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.

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.

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).

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.