**7. Conclusions**

In the review article, we summarize the studies and take information that contributed to elucidating the most widely used biomarkers that produce more information about the di fferent stages of diabetic retinopathy. Currently, there is still no definitive marker for the detection of early stages of DR or even one that can be detected before retinopathy develops. The reviewed studies have suggested a large number of potential markers, however, it must be taken into account that the multifactorial etiology of DR further complicates the detection strategy, so instead of a single definitive marker, the use of a panel or set of markers representing each a ffected aspect in DR. For this, it is necessary to choose a biological matrix that meets characteristics such as accessibility, suitability and representativeness of the disease state. At the ocular level, there are very few biomarkers whose measurement has FDA approval. Most of the biomarkers are exploratory in nature; however. they are very useful for solving issues during drug development. Tears, aqueous humor, and vitreous are among the fluid ocular matrices most frequently used for human biomarker evaluation. The use of these matrices has posed di fficulties, including non-standardized collection processes and little available sample volume. For this reason, it is of grea<sup>t</sup> importance to continue working on studies that provide more information to establish optimized processing and analysis methods in order to make the most of the information obtained from the measurement of biomarkers in them. Large-scale prospective multicenter studies are necessary to be able to accurately determine the veracity and reliability of various biomarkers in the early stages of DR. Therefore, the OS associated with chronic hyperglycemia plays a central role in the stimulation and alteration of the molecular and biochemical signaling pathways along with cellular damage involved in the DR, the evidence suggests that metabolic defects that alter epigenetic substrates they will also a ffect epigenetic chromatin modifications. The epigenetic alterations that were discussed play a critical role in the pathogenesis of DR, further analysis and comparison of the results that have been obtained so far is necessary to also consolidate the path towards the discovery of new treatments and therapeutic strategies.

**Author Contributions:** First, second and thirth chapter preparation, A.K.L.-C. & A.D.R.-C.; fourth and fifth chapter preparation, A.K.L.-C., M.G.M.-R. & S.G.H.-O.; sixth chapter preparation, C.O.-M. & R.R.R.-R.; Figures, A.K.L.-C. & M.G.M.-R.; Tables, A.K.L.-C., M.G.M.-R. & C.O.-M.; Investigation, A.K.L.-C., M.G.M.-R., C.O.-M. & R.R.R.-R.; Original Draft Preparation, A.K.L.-C., M.G.M.-R., C.O.-M., R.R.R.-R. & A.D.R.-C.; Supervision, D.E.A.-S., J.A.C.-G., A.H.-C. & S.G.H.-O.; Project administration, E.G.C.-M. & A.D.R.-C.; Writing-review and editing, All authors. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
