A Hypothesis From Metabolomics Analysis of Diabetic Retinopathy: Arginine-Creatine Metabolic Pathway May Be a New Treatment Strategy for Diabetic Retinopathy

Abstract

Diabetic retinopathy is one of the serious complications of diabetes, which the leading causes of blindness worldwide, and its irreversibility renders the existing treatment methods unsatisfactory. Early detection and timely intervention can effectively reduce the damage caused by diabetic retinopathy. Metabolomics is a branch of systems biology and a powerful tool for studying pathophysiological processes, which can help identify the characteristic metabolic changes marking the progression of diabetic retinopathy, discover potential biomarkers to inform clinical diagnosis and treatment. This review provides an update on the known metabolomics biomarkers of diabetic retinopathy. Through comprehensive analysis of biomarkers, we found that the arginine biosynthesis is closely related to diabetic retinopathy. Meanwhile, creatine, a metabolite with arginine as a precursor, has attracted our attention due to its important correlation with diabetic retinopathy. We discuss the possibility of the arginine-creatine metabolic pathway as a therapeutic strategy for diabetic retinopathy.

Serum metabolomic profiles and semaphorin-3A as biomarkers of diabetic retinopathy progression

“…Therefore, the identification of biomarkers associated with disease progression can be very helpful. 20 Metabolomics is a branch of systems biology and a powerful tool for studying pathophysiological processes, which can aid in identifying the characteristic metabolic changes indicative of DR progression. 21 Therefore, this study intended to analyze and identify serum metabolites and Sema3A levels in DR patients, that could be useful biomarkers of DR progression.…”

“…For completing the cycle, ornithine is then transformed back to arginine. Alternatively, ornithine through the intermediate glutamic γ-semialdehyde may be metabolized to proline 20,34 . Our findings add to the growing body of evidence that alterations in urea cycle metabolites, especially arginine and citrulline, are associated with DR. Arginine also acts as a substrate for the enzyme NOS, which catalyzes a process that results in citrulline and NO; a vasodilator that is essential for maintaining the health of the vascular endothelium.…”

New insight of metabolomics in ocular diseases in the context of 3P medicine

“…In oxygen-induced retinopathy (OIR) mouse model, oral administration of creatine suppressed neovascularization. Several studies revealed the therapeutic potential of creatine supplementation on DR, as well as preventive approaches [ 72 ].…”

“…Second, some of these potential biomarkers have preventive potentials. Some metabolites were identified as protective metabolites for DR by in vitro and in vivo study, such as PGF2α and creatine [ 27 , 72 ]. In fact, most studies only revealed disturbed metabolites in diseases and do not further explore the preventive effects in secondary care.…”

Influence of continuous 4C nursing on quality of life and self-care ability of patients with diabetes retinopathy: An observational study

“…Similarly, surgical intervention, while effective for some complex cases of diabetic retinopathy, carries high risks and recurrence rates. [5–7] Despite significant advancements in medical technology improving visual acuity and quality of life for DR patients posttreatment, the risk of complications such as poor blood sugar control, fundus hemorrhage, and elevated intraocular pressure remains due to a lack of self-care and medication knowledge post-discharge. Therefore, providing effective extended care is crucial to enhance home care effectiveness and improve treatment and rehabilitation levels.…”