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J.B. Jacobs, L.F. Dell'Osso, Z. Wang, G.M. Acland, J. Bennett; Effects of RPR65 Gene Therapy on Nystagmus in Two Canine Littermates: Evidence of a Critical Period for Ocular Motor System (OMS) Calibration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2513.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effects of age at time of administration of gene therapy on the canine model of infantile nystagmus syndrome (formerly known as congenital nystagmus) accompanying RPE65–deficient Leber Congenital Amaurosis.
Two littermates that had similarly characterized nystagmus were treated with AAV–RPE65 at different ages, with one dog receiving a standard dose (10^12 particles/150 microliters) at 10.5 months of age and the other receiving the same dosage at 52 months. Calibrated high–speed videographic ocular motor recordings were made on multiple occasions following treatment and the nystagmus (if present) was analyzed for: waveform; peak–to–peak amplitude; frequency; and eXpanded Nystagmus Acuity Function (NAFX). Receptor function pre– and post–treatment was independently assessed using ERGs, pupilometry or both.
Prior to treatment, both dogs had high–frequency pendular nystagmus and poor receptor function. Based on previously reported results, no effect was expected, nor seen, on the nystagmus prior to three months following treatment. For both dogs, ERGs showed receptor function was significantly restored within 2 months. The nystagmus in the dog treated earlier was shown to have resolved clinically, although the ocular motor recordings showed that there was still a subclinical oscillation present. However there was mimimal change in the nystagmus of the dog treated as an adult.
The differing results for these two littermates who received the same treatment at different times in their development suggests that there may be a critical period during which it is possible to calibrate the OMS. While attempts to overcome afferent deficits beyond this period can lead to increased visual acuity, it may be much more difficult, or may even be no longer possible, for the OMS to recalibrate.
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