**11. Conclusions**

The pathogenesis of DR is complex and likely involves the simultaneous dysregulation of multiple metabolic and signaling pathways throughout the retinal neurovascular unit. Alterations in mitochondrial function has broader consequences than changes in ATP content. Increased oxidative stress and alterations in the redox balance are interrelated mechanisms that are altered by diabetes, and their e ffect on retinal structure and function in diabetes is ye<sup>t</sup> to be explored. The benefit of maintaining retinal energetic flexibility and optimal fuel selection between plentiful competing substrates (glucose versus FA) in diabetes remains largely unexplored, and may represent a promising area of research. Although the present review focuses on the roles of mitochondrial dysfunction and oxidative stress, cellular dysfunction in the retina can take many forms, including neuroinflammation and blood–retinal barrier breakdown. These processes likely occur in parallel and thus future studies should adopt a comprehensive approach that appreciates the interconnectedness of the retina.

**Author Contributions:** Conceptualization, D.J.M., M.A.C., and M.G.R.; resources, D.J.M. and M.G.R.; writing—original draft preparation, D.J.M.; writing—review and editing, M.A.C. and M.G.R.; visualization, D.J.M. and M.G.R.; supervision, M.A.C. and M.G.R.; project administration, M.A.C. and M.G.R.; funding acquisition, M.G.R. All authors reviewed and edited the references. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the American Heart Association, gran<sup>t</sup> number 18AIREA33990023. MGR and DJM were also funded by startup funds and a student research publication grant, respectively, provided by the Central Michigan University College of Medicine.

**Acknowledgments:** We thank Timothy Kern for his feedback during writing the manuscript. We apologize to authors of other important studies that were not included in this review because of space limitations.

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