Importance of the Use of Oxidative Stress Biomarkers and Inflammatory Profile in Aqueous and Vitreous Humor in Diabetic Retinopathy

Abstract

Diabetic retinopathy is one of the leading causes of visual impairment and morbidity worldwide, being the number one cause of blindness in people between 27 and 75 years old. It is estimated that ~191 million people will be diagnosed with this microvascular complication by 2030. Its pathogenesis is due to alterations in the retinal microvasculature as a result of a high concentration of glucose in the blood for a long time which generates numerous molecular changes like oxidative stress. Therefore, this narrative review aims to approach various biomarkers associated with the development of diabetic retinopathy. Focusing on the molecules showing promise as detection tools, among them we consider markers of oxidative stress (TAC, LPO, MDA, 4-HNE, SOD, GPx, and catalase), inflammation (IL-6, IL-1ß, IL-8, IL-10, IL-17A, TNF-α, and MMPs), apoptosis (NF-kB, cyt-c, and caspases), and recently those that have to do with epigenetic modifications, their measurement in different biological matrices obtained from the eye, including importance, obtaining process, handling, and storage of these matrices in order to have the ability to detect the disease in its early stages.

Keywords: antioxidants; aqueous humor; biomarkers of diabetic retinopathy; diabetic retinopathy; metabolic memory; oxidative stress; tear film; vitreous humor.

Figure 1

Reactive oxygen species and antioxidants in the eye. In the eye, chronic hyperglycemic state, atmospheric O2, and inflammation processes alter different metabolic pathways which stimulates the formation of reactive oxygen species (ROS) in the anterior and posterior segment, starting with oxygen (O2) to which the addition of one electron forms the superoxide anion radical (O2-•), the dismutation of this molecule by superoxide dismutases (SOD) forms hydrogen peroxide (H2O2), and the breakdown of this molecule can generate hydroxyl radical (OH•) which is highly reactive. In addition the reaction of O2- • or OH• radical with polyunsaturated fatty acids generates the peroxyl radical (LOO•). The formation of this radicals can be countered by enzymatic and non-enzymatic antioxidants like vitamin C, vitamin E, glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), among others. (Modified from ref. [24]).

Figure 2

Main components in tear film. The wide variety of components in each layer of the tear film provides function, nutrition, and protection to the ocular surface. However, it is susceptible to change their composition due to oxidative stress and inflammatory processes that involve the eye structures, which makes it an easy access ocular matrix to identify these changes measuring levels of components as biomarkers. SOD1: superoxide dismutase-1, Ser: serine, Thr: Threonine, Pro: Proline, IL: Interleukin, sIgA: surface Immunoglobuline A, MMP-9: matrix metalloproteinase-9, TNF-α: Tumor necrosis factor-α. Image created with BioRender.com.