Retbindin: A riboflavin Binding Protein, Is Critical for Photoreceptor Homeostasis and Survival in Models of Retinal Degeneration

Ayse M. Genc; Mustafa S. Makia; Tirthankar Sinha; Shannon M. Conley; Muayyad R. Al-Ubaidi; Muna I. Naash

doi:10.3390/ijms21218083

journal article Open Access Oct 29, 2020

Retbindin: A riboflavin Binding Protein, Is Critical for Photoreceptor Homeostasis and Survival in Models of Retinal Degeneration

Ayse M. Genc Mustafa S. Makia

Tirthankar Sinha

Shannon M. Conley Muayyad R. Al-Ubaidi

Muna I. Naash

International Journal of Molecular Sciences Vol. 21 No. 21 pp. 8083 · MDPI AG

View at Publisher Save 10.3390/ijms21218083

Abstract

The large number of inherited retinal disease genes (IRD), including the photopigment rhodopsin and the photoreceptor outer segment (OS) structural component peripherin 2 (PRPH2), has prompted interest in identifying common cellular mechanisms involved in degeneration. Although metabolic dysregulation has been shown to play an important role in the progression of the disease etiology, identifying a common regulator that can preserve the metabolic ecosystem is needed for future development of neuroprotective treatments. Here, we investigated whether retbindin (RTBDN), a rod-specific protein with riboflavin binding capability, and a regulator of riboflavin-derived cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is protective to the retina in different IRD models; one carrying the P23H mutation in rhodopsin (which causes retinitis pigmentosa) and one carrying the Y141C mutation in Prph2 (which causes a blended cone-rod dystrophy). RTBDN levels are significantly upregulated in both the rhodopsin (Rho)P23H/+ and Prph2Y141C/+ retinas. Rod and cone structural and functional degeneration worsened in models lacking RTBDN. In addition, removing Rtbdn worsened other phenotypes, such as fundus flecking. Retinal flavin levels were reduced in RhoP23H/+/Rtbdn−/− and Prph2Y141C/+/Rtbdn−/− retinas. Overall, these findings suggest that RTBDN may play a protective role during retinal degenerations that occur at varying rates and due to varying disease mechanisms.

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Downregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders

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Metrics

9

Citations

49

References

Details

Published: Oct 29, 2020
Vol/Issue: 21(21)
Pages: 8083
License: View

Authors

A

Ayse M. Genc

Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA

M

Mustafa S. Makia

Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA

T

Tirthankar Sinha

Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA

S

Shannon M. Conley

Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Oklahoma Center for Neurosciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

M

Muayyad R. Al-Ubaidi

Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA; College of Optometry, University of Houston, Houston, TX 77204, USA; Department of Biology and Biochemistry, University of Houston, TX 77204, USA

M

Muna I. Naash

Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA; College of Optometry, University of Houston, Houston, TX 77204, USA; Department of Biology and Biochemistry, University of Houston, TX 77204, USA

Funding

National Eye Institute Award: EY026499, EY10609

national institute of helath Award: GM125528

Cite This Article

Ayse M. Genc, Mustafa S. Makia, Tirthankar Sinha, et al. (2020). Retbindin: A riboflavin Binding Protein, Is Critical for Photoreceptor Homeostasis and Survival in Models of Retinal Degeneration. International Journal of Molecular Sciences, 21(21), 8083. https://doi.org/10.3390/ijms21218083

Retbindin: A riboflavin Binding Protein, Is Critical for Photoreceptor Homeostasis and Survival in Models of Retinal Degeneration

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