Abstract
BackgroundRetinal 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.MethodsReverse 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.ResultsUsing 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.ConclusionsDPOFA 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.
Highlights
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
Before conducting experiments on fluid absorption in bovine RPE-choroid system we wanted to confirm that isoform specificity of Cl-/HCO3- transporter in bovine RPE is similar to that of the human RPE cells, to assure that data obtained in bovine RPE system would be predictive of outcomes in the human retina
The degree of amino acid homology between orthologous human and bovine Cl-/HCO3- isoforms expressed in the RPE was calculated after performing protein alignments using ClustalW2 algorithm
Summary
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. In RD neuro-sensory retina separates from the underlying pigment epithelium due to accumulation of fluid in the subretinal space [4]. Identification of the pharmacological treatment for RD that can be used as adjunctive therapy to improve functional outcomes following surgery and reduce the rate of post-operative complications is of upmost importance. Pharmacological up-regulation of fluid reabsorption from subretinal space to choroid across the retinal pigment epithelium (RPE) has been suggested as potential treatment strategy for retinal detachment [5]. Several drug candidates have been tested in vivo and in vitro for the ability to stimulate subretinal fluid resorption [6,7,8,9,10,11]
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