Quercetin modulates keratoconus metabolism in vitro

Abstract

Corneal scarring is the result of a disease, infection or injury. The resulting scars cause significant loss of vision or even blindness. To-date, the most successful treatment is corneal transplantation, but it does not come without side effects. One of the corneal dystrophies that are correlated with corneal scarring is keratoconus (KC). The onset of the disease is still unknown; however, altered cellular metabolism has been linked to promoting the fibrotic phenotype and therefore scarring. We have previously shown that human keratoconus cells (HKCs) have altered metabolic activity when compared to normal human corneal fibroblasts (HCFs). In our current study, we present evidence that quercetin, a natural flavonoid, is a strong candidate for regulating metabolic activity of both HCFs and HKCs in vitro and therefore a potential therapeutic to target the altered cellular metabolism characteristic of HKCs. Targeted mass spectrometry-based metabolomics was performed on HCFs and HKCs with and without quercetin treatment in order to identify variations in metabolite flux. Overall, our study reveals a novel therapeutic target OF Quercetin on corneal stromal cell metabolism in both healthy and diseased states. Clearly, further studies are necessary in order to dissect the mechanism of action of quercetin.

Differential Effects of Hormones on Cellular Metabolism in Keratoconus In Vitro

“…It has previously been reported that DHEA inhibits the PPP in human endometrial stromal cells 49 and tumor cells 50 . The PPP pathway has also been identified by us as a target of the antioxidant, Quercetin, in HKCs with upregulation of glucose-6-phosphate, glyceraldehyde-3-phosphate, and erythrose-4-phosphate 51 . Treatment of HCFs and HKCs with 2.5 ng/mL and 5 ng/mL DHEA did not cause a significant reduction in PPP intermediates in our model ( Fig.…”

Corneal oxidative damage in keratoconus cells due to decreased oxidant elimination from modified expression levels of SOD enzymes, PRDX6, SCARA3, CPSF3, and FOXM1

“…The antioxidant quercetin is a potential therapy that may address both the elimination of oxidants as well as regulation of metabolism in corneas with KC, considering that excessive lactate production has been associated with oxidative stress and KC. [525354] Future studies should focus on therapeutic agents that can bring the ROS/RNS balance into equilibrium and reduce oxidative damage in corneas with KC.…”

Sulforaphane protects rabbit corneas against oxidative stress injury in keratoconus through activation of the Nrf-2/HO-1 antioxidant pathway

“…It has been reported that the antioxidant riboflavin upregulates the expression of antioxidant compounds in KC stromal cells, downregulates the expression of oxidase genes, and reduces ROS levels in KC ( 18 ). Quercetin may be used to reduce oxidative stress regulatory signals involved in the pathogenesis of KC ( 40 , 41 ). These antioxidative stress drugs may have potential in the clinical prevention and treatment of KC.…”