**1. Introduction**

Diabetic retinopathy (DR) is the most common chronic microvascular complication of uncontrolled diabetes mellitus leading to preventable blindness. Diabetic retinopathy is often classified based on its severity into mild non-proliferative diabetic retinopathy (NPDR), moderate

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR) [1–3]. The major risk factors for developing DR are the duration of diabetes, hyperglycemia, hypertension, and dyslipidemia [4]. Glucose concentration increases in retinal cells leading to saccular capillary microaneurysms, pericyte deficient capillaries, and degenerate capillaries that decrease the retinal perfusion and contribute to the progression of DR [4]. Several types of evidence prove the benefits of tight glycemic and blood pressure control in decelerating the progression of DR. Nevertheless, the numbers of DR patients and the development of DR complications are still increasing, while therapeutic approaches are limited [1, 2].

The immune system plays an important role in the progression of DR. Under hyperglycemic conditions, over activation of the innate immune system takes place, resulting in chronic inflammation of the retina. A study by Urbančič et al. showed the presence of T lymphocytes in the vitreous of patients with PDR. They found that the CD4/CD8 lymphocyte ratio in vitreous is higher compared to the blood ratio in these PDR patients, demonstrating the presence of a local inflammatory process [7]. Prolonged local inflammation in hyperglycemic conditions in the retina may develop into a chronic inflammatory response that is detrimental to the integrity of BRB [6, 8–10]. The destruction of the barrier shifts the retina from its "privileged state" when the BRB functions normally to "compromised state" when the BRB has broken down. Complement system activation also increases in diabetic conditions and this dysregulated activation is known to be involved in the degeneration of retinal vessels. Dysfunctional barriers permit inflammatory molecules and immune cells from systemic circulation to enter the retina and cause further deterioration of the tissue [6, 11]. Cytological examination of the vitreous samples from PDR patients were found to contain significant amounts of macrophages suggesting the infiltration of systemic immune cells into the retina [12, 13]. In addition, there was an increase in adhesion molecule expression and pro-inflammatory cytokine production, suggesting the role of defective neutrophil activity in the

Proliferative Diabetic Retinopathy: An Overview of Vitreous Immune and Biomarkers

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development of chronic inflammation in diabetic retinopathy [14, 15] (**Figure 1**).

**3. Vitreous biomarkers in proliferative diabetic retinopathy**

gression of diabetic retinopathy [5, 6, 18–21] (**Figure 2**).

**Figure 1.** Immune system role in progression of diabetic retinopathy.

**3.1. Biomarkers of oxidative stress**

A biomarker is an objective measurement that is evaluated as an indicator for some complex processes happening in our body [16]. Biomarkers are usually measured to determine the diagnosis and prognosis of some treatments [17]. There are several biomarkers that can be found in diabetic retinopathy patients including biomarkers of oxidative stress, hypoxiainducible factors, angiogenic factors, pro-inflammatory cytokines, chemokines, cell adhesion molecules, and CD200. The value of these biomarkers tells us their possible role in the pro-

The presence of oxidative stress biomarkers indicate an imbalance of reactive oxygen species (ROS) and the functional capabilities of cellular antioxidants [18, 22]. This imbalance can cause

For the last several decades, many studies have been performed in order to better understand DR progression from a molecular viewpoint. The biochemical mechanisms implicated in DR progression have been shown in various animal models and patients with diabetes [1]. It is believed that the involvement of hyperglycemia and hormonal factors in diabetic patients could disturb hemostasis in the retina and change the balance of some mediators including growth factors, cytokines, inflammatory, and adhesion molecules [5]. These changes result in altered capillary permeability, apoptosis of capillary cells, and angiogenesis, leading to DR complications [3]. With improved clarity of molecular pathways in DR pathophysiology, the advancement of selective therapeutic approaches could be discovered and the management of DR could be more effective [1, 5]. This chapter focuses on the inflammatory molecules and biomarkers involved in the pathophysiology of DR.
