title: DPOFA, a Cl⁻/HCO₃⁻ exchanger antagonist, stimulates fluid absorption across basolateral surface of the retinal pigment epithelium.
abstract: BACKGROUND
  Retinal detachment is a disorder of the eye in which sensory retina separates from the retinal pigment epithelium (RPE) due to accumulation of fluid in subretinal space. Pharmacological stimulation of fluid reabsorption from subretinal space to choroid across the RPE has been suggested as a treatment strategy for retinal detachment. DPOFA, (R)-(+)-(5,6-dichloro 2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy]acetic acid, is an abandoned drug capable of inhibiting Cl⁻/HCO₃⁻ exchanger activity. We hypothesized that DPOFA may increase fluid absorption across basolateral surface of the RPE.
  
  
  METHODS
  Reverse transcription polymerase chain reaction (RT-PCR) analysis of mRNA for six different transporters that may act as Cl⁻/HCO₃⁻ exchangers was conducted in bovine and human RPE to confirm that RPE from two species expresses the same repertoire of Cl⁻/HCO₃⁻ exchanger isoforms. The degree of amino acid homology between orthologous human and bovine RPE-specific isoforms was calculated after performing protein alignments. Transport of fluid across bovine RPE-choroid explants mounted in the Ussing chamber was used to assess the ability of DPOFA to modulate fluid absorption across the RPE.
  
  
  RESULTS
  Using RT-PCR we showed that three isoforms (SLC4A2, SLC4A3, and SLC26A6) are strongly expressed in human and bovine RPE preparations. Amino acid comparisons conducted for RPE-specific isoforms support the use of bovine RPE-choroid explants as an adequate experimental system for assessing fluid absorption activity for DPOFA. Our data is consistent with the fact that DPOFA stimulates fluid absorption across the RPE in bovine RPE-choroid explants.
  
  
  CONCLUSIONS
  DPOFA seems to stimulate transport of water across the RPE in bovine RPE-choroid explants. Additional experiments are required to establish dose-dependent effect of DPOFA on fluid absorption in the bovine RPE-choroid experimental system.
authors.affiliation: Department of Ophthalmology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Iserovich
authors.forename: Qiong
authors.initials: Q
authors.lastname: Qin
authors.forename: Konstantin
authors.initials: K
authors.lastname: Petrukhin
mesh_terms: D000042:Absorption; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002417:Cattle; D027963:Chloride-Bicarbonate Antiporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005449:Fluorenes / Q000494:pharmacology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000378:metabolism
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D005449:Fluorenes; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D014867:Water; C053396:L 644711
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