RGD Reference Report - Impact of P-glycoprotein on blood-retinal barrier permeability: comparison of blood-aqueous humor and blood-brain barrier using mdr1a knockout rats. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Impact of P-glycoprotein on blood-retinal barrier permeability: comparison of blood-aqueous humor and blood-brain barrier using mdr1a knockout rats.

Authors: Fujii, S  Setoguchi, C  Kawazu, K  Hosoya, K 
Citation: Fujii S, etal., Invest Ophthalmol Vis Sci. 2014 Jul 1;55(7):4650-8. doi: 10.1167/iovs.13-13819.
RGD ID: 11062172
Pubmed: PMID:24985475   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.13-13819   (Journal Full-text)

PURPOSE: The purpose of this study was to clarify the impact of P-glycoprotein (P-gp) on blood-retinal barrier (BRB) and blood-aqueous humor barrier (BAB) permeability, in contrast to blood-brain barrier (BBB) permeability. METHODS: Permeabilities of six compounds, including P-gp substrates (quinidine, digoxin, and verapamil), were investigated in wild-type and mdr1a knockout rats using retinal, aqueous humor, and brain uptake index (RUI, AHUI, and BUI, respectively) methods and integration plot analysis. RESULTS: In both rat strains, quinidine, digoxin, and verapamil were transported by P-gp across each barrier; however, the impact of P-gp on retinal uptake of quinidine and verapamil was less pronounced than that on brain uptake. The apparent influx permeability clearance (Kin) values of verapamil in retina obtained from wild-type and knockout rats were similar (0.824 +/- 0.201 and 0.849 +/- 0.980 mL/min.g retina, respectively; mean +/- SD; n = 3 rats). The Kin in aqueous humor and brain obtained from knockout rats was, respectively, 3-fold and 12-fold higher than that of wild-type (P < 0.05). In P-gp-deficient conditions, the RUI and AHUI of quinidine, digoxin, and verapamil, as well as the BUI of quinidine and digoxin, were decreased by P-gp inhibitors. However, the BUI of verapamil was not changed by P-gp inhibitors. Results suggest that carrier-mediated influx transporters exist in the blood-ocular barriers and that the function of verapamil influx transporters is markedly different between the retina and brain. CONCLUSIONS: In both rat strains, P-gp operates in the blood-ocular barriers, and the impact of P-gp on BRB permeability to quinidine and verapamil is lower than that on BBB permeability.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abcb1aRatestablishment of blood-retinal barrier  IMP  RGD 


Objects Annotated

Genes (Rattus norvegicus)
Abcb1a  (ATP binding cassette subfamily B member 1A)


Additional Information