Is successful gene therapy for retinal disease in sight?

Abstract

The correction of a genetic defect by the transfer and expression of a non-mutated version of the effected gene is the basis of most gene replacement strategies. However, predicting whether this will be sufficient to restore cell function and alter the progress of a given disease can be hard particularly when dealing with something as complex as the eye and vision. Thus, it is exciting to see the recent results of Ali and co-workers 1 Ali R.R. et al. Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat. Genet. 2000; 25: 306-310 Crossref PubMed Scopus (292) Google Scholar describing gene therapy for retinal degeneration by expression of the Prph-2 gene that encodes the peripherin-2 membrane protein required for the stabilization of the outer segment discs of photoreceptor cells. In this study an adeno-associated viral vector expressing peri-pherin-2 under the control of the rhodopsin promoter was administered by sub-retinal injection to Prph-2 mutant mice – a well-characterized model of retinal degeneration. Analysis of the retinas of treated mice showed structural (the formation of outer segments), biochemical (increased concentrations of rhodopsin) and physiological (electroretinal responses to light) changes consistent with correction of a significant number (approximately 30%) of photoreceptor cells. This data indicates that function can be restored to a well-differentiated cell (the photoreceptor) albeit at this stage in relatively young (10-day-old) animals. It will be interesting to see if gene transfer of the Prph-2 gene can now be used to rescue older mice with more established retinal degeneration and also to see whether long-term exogenous expression can be used to maintain or even restore vision.