Naash, Muna I.2020-06-04May 20202020-05May 2020Portions of this document appear in: Sinha, Tirthankar, Mustafa Makia, Jianhai Du, Muna I. Naash, and Muayyad R. Al-Ubaidi. "Flavin homeostasis in the mouse retina during aging and degeneration." The Journal of nutritional biochemistry 62 (2018): 123-133. And in: Sinha, Tirthankar, Muayyad R. Al-Ubaidi, and Muna I. Naash. "Flavin Imbalance as an Important Player in Diabetic Retinopathy." In Retinal Degenerative Diseases, pp. 575-579. Springer, Cham, 2019. And in: Sinha, Tirthankar, Muna I. Naash, and Muayyad R. Al-Ubaidi. "The symbiotic relationship between the neural retina and retinal pigment epithelium is supported by utilizing differential metabolic pathways." Iscience (2020): 101004.https://hdl.handle.net/10657/6684Retbindin is a novel retina specific riboflavin binding protein, ablation of which leads to degeneration. Using a combination of untargeted steady state metabolomics and targeted flux metabolomics, we here investigated the mechanism behind this degeneration. Furthermore, the neural retina (NR) and retinal pigment epithelium (RPE) maintain a symbiotic metabolic relationship, disruption of which leads to debilitating vision loss. In the current study we have identified the differences in the steady state metabolite levels and the pathways functioning between bona fide NR and RPE. Moreover, involvement of key metabolic cofactors, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) in cellular homeostasis has been well established for tissues other than the retina. Here, we present an optimized method to effectively extract and quantify FAD and FMN from a single neural retina and its corresponding RPE. We also show that in absence of retbindin there is significant reduction of flavins in both the neural retina and RPE, causing an imbalance in their symbiosis. However, there is no report on how the retina responds to riboflavin deficiency. Thus, here we developed a diet induced model of riboflavin deficiency and identified how that results in metabolic dysfunction in both the neural retina and RPE. We have further shown that these metabolic abnormalities can eventually compromise the electrophysiological response of both the neural retina and the RPE. Thus, we provide evidence how riboflavin and its binding protein retbindin can help in regulating retinal homeostasis.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).retinametabolismneural retinaRPEretinal pigment epitheliumriboflavinFADFMNHPLCmetabolomicsage related macular degeneration (AMD)diabetic retinopathy (DR)MacTelserinePHGDHserine biosynthesisglucose metabolismfatty acid metabolismsphingolipidceramideretbindinPkm2mitochondriaRetinitis PigmentosaInherited retinal disordersBVVLSFazio-Londe SyndromeAriboflavinosisflavinsriboflavin binding proteinriboflavin carrier proteinneurodegenerationretinal degenerationmachine learningomics2020-06-04Thesisborn digital