Abstract
Purpose :
Oxidative stress crucially contributes to optic neuropathy development by disrupting the balance between reactive oxygen species production and antioxidants. Non-arteritic anterior ischemic optic neuropathy (NAION), a prevalent acute blinding condition in those over 50, lacks a well-understood mechanism and effective treatment. This study investigates the influence of the reactive metabolite methylglyoxal (MGO) on retinal and optic nerve changes induced by photochemical thrombosis in an animal model, considering its association with NAION and metabolic stress.
Methods :
We initially supplemented 0.5% MGO in water for four weeks before inducing a photochemical thrombosis NAION model in C57BL/6J mice (6-8 weeks old) using a 577 nm laser. In vivo imaging of the retina and optic nerve was assessed using optical coherence tomography at baseline, day 3, and 21. Immunohistochemistry was conducted to assess changes in the expression of OPA-1, Iba-1, GFAP, and Brn3a antibodies in the retina and optic nerve. Moreover, visual function was evaluated through optokinetic response (OKR) at baseline, day 7, and 21. Two-tailed Student's t-test was used for statistical analysis in comparison with control group without MGO.
Results :
Three days post-NAION induction, peripapillary ganglion cell complex (GCC) thickened from baseline (Baseline: 77.8 ± 1.92 mm; Day-3: 89.2 ± 2.17 mm, p<0.01). By day twenty-one, OCT revealed GCC thinning (70.2 ± 1.92, p<0.01), indicating retinal ganglion cell loss, confirmed by a 34% decrease in Brn3a+ cells (p<0.01). Retinal staining in the experimental group showed a significant increase in the expression of mitochondrial fusion protein OPA-1, disruption of which can cause mitochondrial dysfunction, and microglial marker Iba-1, which plays role in neuroinflammation (p<0.01). However, astroglial injury marker GFAP showed no significance (p=0.52). Additionally, OKR-determined visual thresholds gradually reduced significantly in the experimental group (p<0.05).
Conclusions :
Our results suggest that methylglyoxal exacerbates the pathology of NAION, potentially through redox modulation of mitochondrial proteins and causing damage to retinal cells. Further investigation into cellular ultrastructural changes and strategies to mitigate metabolic stress may unveil novel treatments for this vision-threatening disease.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.