The importance of biomarkers of neurodegeneration in diabetic retinopathy

Relevance Diabetic retinopathy (DR) is one of the leading causes of severe visual impairment in patients with diabetes mellitus. In the context of the growing incidence of diabetes, an important aspect is not only the detection of vascular changes, but also the assessment of neurodegenerative processes leading to deterioration of the functional capabilities of the retina [1, 2]. Modern diagnostic methods, such as optical coherence tomography (OCT), optical coherence tomography-angiography, microperimetry, fundus photography, fluorescence angiography (FA), as well as molecular markers (cytokines, growth factors, etc.) allow obtaining detailed information on structural and functional changes, which opens up prospects for the use of biomarkers in predicting the course of DR and assessing the response to treatment [3, 4]. Objective To summarize current literature data on the role of both molecular and visualized biomarkers of neurodegeneration in the pathogenesis and prognosis of diabetic retinopathy, and to assess their potential for use in clinical practice. Material and Methods The paper presents a comprehensive review of current studies devoted to the identification and evaluation of biomarkers characterizing neurodegenerative changes in DR. The publications reviewed included methods of enzyme immunoassay of biological fluids (serum, lacrimal fluid, vitreous body) and data from non-invasive imaging methods (OCT, OCT angiography, microperimetry, fundus photography, fluorescein angiography). The review includes a classification of biomarkers by their functional role (predictive, diagnostic, prognostic) and by the method of registration (molecular and visualized). Results The review showed that the key molecular biomarkers associated with neurodegeneration in DR are: • VEGF-A is the main stimulator of angiogenesis, whose increased expression correlates with deterioration of anatomical and functional parameters; • PlGF is a secondary but proinflammatory factor involved in the regulation of metabolic processes; • PEDF is a neuroprotective and antiangiogenic protein that can compensate for the effects of VEGF; • TNF-α, IL-1β, TGF-β and NGF are cytokines that reflect the inflammatory status and neuroprotective mechanisms. Visualized biomarkers obtained using modern methods include: • measurements of the thickness of the nerve fiber layer (RNFL) and disorganization of the inner retinal layers (DRIL); • assessment of the integrity of the ellipsoidal zone; • microperimetry parameters characterizing local light sensitivity; • and parameters obtained using OCT angiography (e.g. FAZ area, vascular density). Conclusion Comprehensive analysis of both molecular and visualized biomarkers allows not only to determine the stage of the disease, but also to predict its dynamics, which opens up opportunities for an individual approach to DR therapy. However, the ambiguity of the results of individual studies emphasizes the need for further prospective clinical studies to standardize the use of these indicators in everyday practice. Key words: diabetes mellitus; diabetic retinopathy; neurodegeneration; biomarkers; neurodegenerative biomarkers