Figure 4. Summary of different proposed underlying protective and detrimental mechanisms causing diabetic macular edema (DME) in diabetic patients. The metabolites in the green boxes with thin blue arrows represent insufficiency of the system to work against oxidative stress, maintain the extracellular matrix, support energy production, and healing inflammation. These phenomena were revealed by decreased antioxidants, activated biotin pathway, elevated extracellular matrix constituents, and increased activated immune signalling sphingosine-1-phosphate pathway which involved in healing the eye of DME patients. The red box and thick arrow indicate the pathogenesis, oxidative stress, hyperglycemia, and inflammation, as implied by the associated metabolites causing the ocular tissue damage in DME patients. The blue oval indicates the involved damaged tissues/organelles found in this study, and the metabolites suggest corresponding tissue damage.