Metabolomics Analysis of Human Vitreous in Diabetic Retinopathy and Rhegmatogenous Retinal Detachment

The vitreous humor is a highly aqueous
eye fluid interfacing with
the retina and lens and providing shape. Its molecular composition
provides a readout for the eye’s physiological status. Changes
in cellular metabolism underlie vitreoretinal pathologies, but despite
routine surgical collection of vitreous, only limited reports of metabolism
in the vitreous of human patients have been described. Vitreous samples
from patients with rhegmatogenous retinal detachment (n = 25) and proliferative diabetic retinopathy (n = 9) were profiled along with control human vitreous samples (n = 8) by untargeted mass-spectrometry-based metabolomics.
Profound changes were observed in diabetic retinopathy vitreous, including
altered glucose metabolism and activation of the pentose phosphate
pathway, which provides reducing equivalents to counter oxidative
stress. In addition, purine metabolism was altered in diabetic retinopathy,
with decreased xanthine and elevated levels of related purines (inosine,
hypoxanthine, urate, allantoate) generated in oxidant-producing reactions.
In contrast, the vitreous metabolite profiles of retinal detachment
patients were similar to controls. In total, our results suggest a
rewiring of vitreous metabolism in diabetic retinopathy that underlies
disease features such as oxidative stress and furthermore illustrates
how the vitreous metabolic profile may be impacted by disease.