Ablation of Retbindin, the Riboflavin Binding Protein, Exacerbates Retinal Degenerative Phenotypes in Mouse Models of Human Retinal Diseases
type: CreativeWork
description: Retbindin (Rtbdn) is a retina-specific, riboflavin binding protein, expressed only by the rod photoreceptor cells. Riboflavin is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which are essential co-factors for enzymes involved in wide-range of metabolic processes. Since flavins are directly linked to the metabolism and metabolic dysregulation is a hallmark of degeneration, we hypothesized that Rtbdn, as a riboflavin binding protein, plays a role in modulating the degenerative process. In support of our hypothesis, we found that Rtbdn is significantly upregulated in the retinas of mouse models of late-onset cone rod dystrophy (Prph2R172W), retinitis pigmentosa (RhoP23H/+) and pattern dystrophy (Prph2Y141C/+). We investigated the effect of Rtbdn ablation in these retinal degenerative models in order to elucidate the function of this novel protein in retinal health and disease. Although, the ablation of Rtbdn alone (Rtbdn-/-) had no deleterious effects on retinal function up to postnatal day (P) 120, eliminating Rtbdn in the models led to significant reductions in both scotopic and photopic electroretinographic amplitudes, compared to the single mutants. Histologic assessments revealed severe thinning of diseased retinas upon elimination of Rtbdn. While the outer nuclear layer (ONL) cell counts in wild type (WT) and Rtbdn-/- were not significantly different from each other, we observed significant loss of ONL cells in the Prph2R172W/Rtbdn-/-, RhoP23H/+/Rtbdn-/-, and Prph2Y141C/+/Rtbdn-/- in comparison to the single mutants. Ultrastructural analyses revealed shorter, malformed and disorganized photoreceptor outer segments, swollen inner segments and dilated Bruch’s membrane in the retinas of degenerative models in absence of Rtbdn. In addition, elimination of Rtbdn in the diseased retina led to vascular pathologies and appearance of neovascular tufts secondary to cell loss. We observed model-dependent alterations in the riboflavin, F…
abstract: Retbindin (Rtbdn) is a retina-specific, riboflavin binding protein, expressed only by the rod photoreceptor cells. Riboflavin is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which are essential co-factors for enzymes involved in wide-range of metabolic processes. Since flavins are directly linked to the metabolism and metabolic dysregulation is a hallmark of degeneration, we hypothesized that Rtbdn, as a riboflavin binding protein, plays a role in modulating the degenerative process. In support of our hypothesis, we found that Rtbdn is significantly upregulated in the retinas of mouse models of late-onset cone rod dystrophy (Prph2R172W), retinitis pigmentosa (RhoP23H/+) and pattern dystrophy (Prph2Y141C/+). We investigated the effect of Rtbdn ablation in these retinal degenerative models in order to elucidate the function of this novel protein in retinal health and disease. Although, the ablation of Rtbdn alone (Rtbdn-/-) had no deleterious effects on retinal function up to postnatal day (P) 120, eliminating Rtbdn in the models led to significant reductions in both scotopic and photopic electroretinographic amplitudes, compared to the single mutants. Histologic assessments revealed severe thinning of diseased retinas upon elimination of Rtbdn. While the outer nuclear layer (ONL) cell counts in wild type (WT) and Rtbdn-/- were not significantly different from each other, we observed significant loss of ONL cells in the Prph2R172W/Rtbdn-/-, RhoP23H/+/Rtbdn-/-, and Prph2Y141C/+/Rtbdn-/- in comparison to the single mutants. Ultrastructural analyses revealed shorter, malformed and disorganized photoreceptor outer segments, swollen inner segments and dilated Bruch’s membrane in the retinas of degenerative models in absence of Rtbdn. In addition, elimination of Rtbdn in the diseased retina led to vascular pathologies and appearance of neovascular tufts secondary to cell loss. We observed model-dependent alterations in the riboflavin, F…
author: Genc, Ayse Mine
language: eng
keywords: Retbindin, Flavin, Retina, Peripherin2, Rhodopsin, Mouse model, Retinal degeneration
date published: 2020-05
date modified: 2026-07-24T02:31:42Z
provider: University of Houston
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Houston

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property ID: Handle
value: https://hdl.handle.net/10657/6700