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

Autor: Shannon M. Conley, Muayyad R. Al-Ubaidi, Muna I. Naash, Ayse M Genc, Mustafa S Makia, Tirthankar Sinha
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Retinal degeneration
Male
rho GTP-Binding Proteins
genetic structures
Peripherins
lcsh:Chemistry
chemistry.chemical_compound
Mice
0302 clinical medicine
Homeostasis
lcsh:QH301-705.5
Spectroscopy
Mice
Knockout
biology
inherited retinal degeneration
Retinal Degeneration
General Medicine
Photoreceptor outer segment
Computer Science Applications
Cell biology
Rhodopsin
Female
Prph2
Photoreceptor Cells
Vertebrate
Flavoprotein
Catalysis
Article
Retina
Riboflavin binding
Inorganic Chemistry
03 medical and health sciences
Retinitis pigmentosa
medicine
Animals
Physical and Theoretical Chemistry
riboflavin
Peripherin 2
Eye Proteins
Molecular Biology
flavoproteins
Organic Chemistry
Retinal
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
chemistry
lcsh:Biology (General)
lcsh:QD1-999
rhodopsin
Mutation
030221 ophthalmology & optometry
biology.protein
sense organs
metabolism
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 8083, p 8083 (2020)
Volume 21
Issue 21
ISSN: 1422-0067
Popis: 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&minus
/&minus
and Prph2Y141C/+/Rtbdn&minus
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.
Databáze: OpenAIRE
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