Retbindin: A riboflavin Binding Protein, Is Critical for Photoreceptor Homeostasis and Survival in Models of Retinal Degeneration
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 dysregulati...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/21/8083 |
| Summary: | 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 <i>Prph2</i> (which causes a blended cone-rod dystrophy). RTBDN levels are significantly upregulated in both the rhodopsin (<i>Rho</i>)<i><sup>P23H/+</sup></i> and <i>Prph2<sup>Y141C/+</sup></i> retinas. Rod and cone structural and functional degeneration worsened in models lacking RTBDN. In addition, removing <i>Rtbdn</i> worsened other phenotypes, such as fundus flecking. Retinal flavin levels were reduced in <i>Rho<sup>P23H/+</sup>/Rtbdn<sup>−/−</sup></i> and <i>Prph2<sup>Y141C/+</sup>/Rtbdn<sup>−/−</sup></i> 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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| ISSN: | 1661-6596 1422-0067 |