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Editors Selection IGR 11-2
Medical treatment: Drug delivery to inner wall of Schlemm's Canal
Comment by Terete Borras on:
17970 Targeted gene transfer to Schlemm's canal by retroperfusion, Stamer DW; Chan DW; Ross Ethier C, Experimental Eye Research, 2007; 84: 843-849
Stamer et al. (706) seek to preferentially target gene transfer to SC and JCT cells of the human trabecular meshwork by a technique called 'retroperfusion'. This technique was developed by author to deliver drugs to the innerwall of the SC (Ethier, IOVS 1993; 34: 385). Since then, this technique has been used only in three publications, all from their own laboratory. The technique consists in sealing an area of the anterior segment posterior to the limbus with a plastic 'fence', and filling the resulting reservoir with the drug. The procedure continues by lowering the pressure of the anterior chamber to -1 mmHg for 30-60 min and maintaining it at 0 mmHg for another 30-60min. After this retroperfusion, the eyes are forward perfused with standard medium. Here, the authors used human eyes, the perfusion anterior chamber developed by DH Johnson (IOVS 1987; 28: 954), and recombinant adenoviruses (Ads) with a reporter transgene. They compared the retroperfusion delivery method to their own procedures of injecting the virus through the incoming tubing of the perfusion chamber.
The authors state that standard Ad delivery does not transduce efficiently JCT or SC cells, which does not seem to occur in any of the papers they cite (nor in those they don't). Even if this wrong conclusion precludes in part the purpose of their study, a delivery site closer to the SC and JCT would always favor transduction of those cells. It is well-established in the gene transfer field that the local injection site exhibits always higher levels of gene transduction.
Their results show preferential SC and JCT delivery, rather than a 'delivery limited to those cells', as they claim. Their experimental design does not allow full support of their conclusions. For a proper comparison, the same concentration and volume of viruses should have been used in forward and retroperfusions, which it was not. Further, to claim transduction by retroperfusion, anterior segments needed to be exhaustively washed of the virus and remounted in fresh chambers before the forward perfusion time. An indication that the transgene expression observed might not had been the result of just retroperfusion is the fact that the length of retroperfusion time might have not been quite enough to support complete Ad cell entry.
Recombinant Ads are ideal to follow fluid dynamics in the TM. Although standard perfusions do not seem to have the drawbacks mentioned here, the simple retroperfusion methods presented, if refined and confirmed, could provide a niche to study in vitro certain properties of the TM cells.
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