<p>Targeting Netrin-1 and -4 as a Novel Diagnostic Parameter and Treatment Option for Diabetic Retinopathy</p>

Abstract

Diabetic retinopathy (DR) is a retinal vascular disorder associated with both type 1 and type 2 diabetes mellitus (DM). It is characterized by specific loss of pericytes, which leads to an augmented blood vessel permeability, and development of new blood vessels (retinal neovascularization). Moreover, stiffening of eye membrane, inflammation, and apoptosis of endothelial cells also lead to damage of the blood-retinal barrier and blindness in most cases unless it's detected and managed early. Hence, this review was intended to assess the potential roles of Netrin-1 and-4 as new/alternative biomarkers and therapeutic options for DR. Netrin-1 and-4 have been the most known ligands and are well known for their role in neural guidance. DR has both neural and vascular components; therefore, biomarkers used for both neural and vascular retinal tissues are potentially important. According to different experimental and clinical studies, as compared to the normal groups, there was a significant increment in both retinal Netrin-1 and-4 mRNA and protein levels in the retinopathy groups. In addition, exogenous supplementation of these proteins is also used as a therapeutic agent for DR.

Anti-Inflammatory Role of Netrin-4 in Diabetic Retinopathy

“…Targeting VEGF-A, however, is not always beneficial to the patients and is only effective at the late stages of disease when the damage cannot be repaired [ 14 ]. A recent work revisited the knowledge on NTN4 and other netrin receptors in DR and emphasized the number of basic research studies that could have a translational impact in using netrins as DR biomarkers [ 15 ]. However, little is known of its role in DR and/or if netrins can play a role at earlier stages of the pathology.…”

The relationship between plasma serglycin levels and the diagnosis of diabetic retinopathy

“…For instance, Li et al found that angiogenesis growth factors VEGFC, ANGPT1, ANGPT2, and EFNB2 were upregulated in DR patients, presenting their potentials as biomarkers for DR diagnosis and treatment. 15 Another report demonstrated that netrin-1 and netrin-4 were overexpressed in the DR group, functioning as promising therapeutic agents for DR. 16 Serglycin (SRGN) was a hematopoietic granulosa protein-polysaccharide composed of a relatively small (*17 kDa) core protein. 17 Studies showed that SRGN was mainly expressed in normal hematopoietic cells, endothelial cells, uterine decidua, and embryonic stem cells.…”