Effect of Co-enzyme Q10 eyedrops on neurodegeneration and mitochondrial dysfunction in the retina of a type 2 diabetic mice model

Purpose : Current treatments for diabetic retinopathy (DR), one of the leading causes of blindness and vision impairment, are invasive and possess several limitations. Developing new treatment regimens to arrest its development and progression to proliferative stage to preserve vision is imperative. Mitochondrial dysfunction has been implicated in the pathogenesis of DR. Here, we test the effect of Coenzyme Q10 (CoQ10) eyedrops, a proven antioxidant and mitochondrial stabilizer, on DR with a type 2 diabetic mouse model as to investigate the potential of CoQ10 eyedrops as a non-invasive treatment option for DR.

Methods : Male C57BL/KsJ-db/db (db/db) mice aged 9 weeks with fasting blood glucose levels ≥ 13.9 mmol/L were used. CoQ10 eyedrops conjugated with Vitamin E TPGS were instilled twice daily to the treatment group (CoQ10, n=7), and PBS was given to the control group (control, n=6). After 4 months of treatment, the retinas of the mice were harvested to assess the morphology and ex-vivo mitochondrial bioenergetics with immunohistochemistry and the Seahorse XFe24 analyzer, respectively.

Results : The db/db mice treated with CoQ10 eyedrops were found to have thicker outer (ONL) and inner nuclear layers (INL) compared to the control mice (ONL: control=53.6±2.0 μm vs. CoQ10=60.3±2.0 μm, p=0.038; INL: control=30.9±1.6 μm vs. CoQ10=39.0±0.6 μm, p=0.002). Their retinas were also found to have a higher photoreceptor (control=316.4±14.4 vs. CoQ10=380.8±18.0, p=0.019) and cone cell density (control=28.8±4.1 vs. CoQ10=43.8±2.1, p=0.006) than the control. The retina of CoQ10 treated db/db mice also exhibited stronger mitochondrial functions compared to the control (Basal respiration:1.37±0.14-fold, p=0.044; Maximal respiration: 1.59±0.15-fold, p=0.031; Spare capacity: 6.13±0.90-fold, p=0.003).

Conclusions : Our data indicates that CoQ10 eyedrops ameliorated retinal neurodegeneration and associated mitochondrial dysfunction in diabetic mice. It provides further insight on the role of mitochondrial dysfunction in the pathogenesis of diabetic retinopathy and suggests that CoQ10 eyedrops may be a potential therapeutic option for DR-related neuropathy.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.