**Author details**

*Visual Impairment and Blindness - What We Know and What We Have to Know*

regulation of genes related to glycolysis [63–65].

reactions is expected to result.

contains no introns that also increases its susceptibility to oxidative damage. Meanwhile, mtDNA mainly encodes electron transport chain proteins, including ATP synthase, cytochrome b, cytochrome c oxidase, and NADH dehydrogenase. Damaged mtDNA will lead to impaired electron transport chain proteins, further deteriorating cell energy production, generating more ROS, and inducing extra damages to mtDNA. Previous studies have revealed that abnormal mtDNA leads to reduced energy production and initiation of apoptosis [59–62]. Loss of mtDNA in ARPE-19 cells led to the change of nuclear gene expression, especially the up-

The mitochondrial-nuclear crosstalk could be a mechanism that the RPE cell uses to compensate the insufficient energy productions due to the mitochondrial dysfunction. Other changes in nuclear gene expressions caused by loss of mtDNA include up-regulation of proteins related to uptake of ROS and drusen, extracellular matrix and matrix enzymes, lipid transport-related proteins, and inflammation-related regulators. Therefore, damaged mtDNA has been considered as an important biomarker of oxidative stressed RPE and progression of AMD [50, 66, 67]. Fragments of mtDNA have been found to migrate to the nucleus and be inserted into the nuclear genome [68–71]. The entrance of mitochondria into the nucleus has been reported to promote both the attack of mitochondria by nuclear protein and the attack of nuclear DNA and protein by protein of the mitochondrial intermembrane space [65, 68–74]. Mitochondria move to the nucleus under stress to fulfill energy demand of the nucleus.

Therefore, our observation that mitochondria entering the nucleus could be one of the mechanisms to explain mitochondrial diseases and the aging process. Our AMD interactome map implies that a positive correlation exists between AMD mechanism and early oxidative stress biomarkers, as well as inflammation switch, apoptosis, transcriptional regulation, and mitochondrial dysfunction [26, 32, 52, 75–77]. The mechanistic dissection of our AMD interactome map is the initial delineation of the underlying physiology of oxidative stress-mediated phosphorylation signaling in RPE apoptosis which can lead to AMD progression. In addition, the phosphoprotein interactome provides a stimulus for understanding oxidative stress-induced mitochondrial changes and the mechanism of aggregate formation induced by protein phosphorylations. As a consequence, an effective therapeutic approach to treat AMD based on the modulation of phosphorylation

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Weilue He1 , Srinivas R. Sripathi<sup>2</sup> , Madu Joshua3 , Ruonan Zhang4 , Fabunmi Tosin3 , Patrick Ambrose3 , Diana R. Gutsaeva<sup>5</sup> and Wan Jin Jahng3 \*

1 Department of Biomedical Engineering, Michigan Technological University, Houghton, MI, USA

2 Department of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

3 Retina Proteomics Laboratory, Department of Petroleum Chemistry, American University of Nigeria, Yola, Adamawa, Nigeria

4 Department of Ophthalmology, University of South Carolina, Columbia, SC, USA

5 Department of Ophthalmology, Augusta University, Augusta, GA, USA

\*Address all correspondence to: wan.jahng@aun.edu.ng

© 2019 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.
