Expression profiling after retinal detachment and reattachment: a possible role for aquaporin-0.
OBJECTIVE
Retinal detachment (RD) is associated with acute visual loss caused by anatomic displacement of the photoreceptors and with chronic visual loss/disturbance caused by retinal remodeling and photoreceptor cell death, which may occur even after successful reattachment. The P2Y(2) receptor agonist INS37217 improves the rate of retinal reattachment in animal models of induced RD, and has been shown to also significantly enhance the rate of ERG recovery in a mouse model of RD. The identification of genes modulated by INS37217 may allow further drug discovery for treating RD and edema.


METHODS
To identify genes involved in RD and subsequent reattachment, a retinal microarray screen was performed using a mouse model of RD in the presence or absence of INS37217.


RESULTS
Ninety-two genes were identified as differentially expressed across three time points, most of which were upregulated in the presence of this agonist. Furthermore, it was shown that RD alters the expression of aquaporin-0 (AQP-0), and this modulation is prevented by treatment with INS37217. The presence of AQP-0 in retinal bipolar cells was also demonstrated, whereas it was previously thought to be specific to the lens. Mice lacking functional alleles of AQP-0 had a phototransduction deficit as assessed by electroretinography; however, their photoreceptor structure was normal, indicative of a problem with signal transmission between neurons.


CONCLUSIONS
This study establishes the genes involved in RD and reattachment, and also demonstrates for the first time a physiologically significant role for AQP-0 in retinal function.
Farjo
Rafal
R
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Peterson
Ward M
WM
Naash
Muna I
MI
D000818:Animals; D020346:Aquaporins / Q000235:genetics*; D003845:Deoxycytosine Nucleotides / Q000494:pharmacology; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012163:Retinal Detachment / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014529:Uridine / Q000031:analogs & derivatives / Q000494:pharmacology
D020346:Aquaporins; D003845:Deoxycytosine Nucleotides; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C030328:aquaporin 0; C465279:denufosol tetrasodium; D014529:Uridine