A demonstration of cone function plasticity after gene therapy in achromatopsia.

Recent advances in regenerative therapy have placed the treatment of previously incurable eye diseases within arms' reach. Achromatopsia is a severe monogenic heritable retinal disease that disrupts cone function from birth, leaving patients with complete colour blindness, low acuity, photosensitivity and nystagmus. While successful gene-replacement therapy in non-primate models of achromatopsia has raised widespread hopes for clinical treatment, it was yet to be determined if and how these therapies can induce new cone function in the human brain. Using a novel multimodal approach, we demonstrate for the first time that gene therapy can successfully activate dormant cone-mediated pathways in children with achromatopsia (CNGA3- and CNGB3-associated, 10-15 years). To test this, we combined functional MRI population receptive field mapping and psychophysics with stimuli that selectively measure cone photoreceptor signalling. We measured cortical and visual cone function before and after gene therapy in four paediatric patients, evaluating treatment-related change against benchmark data from untreated patients (n = 9) and normal-sighted participants (n = 28). After treatment, two of the four children displayed strong evidence for novel cone-mediated signals in visual cortex, with a retinotopic pattern that was not present in untreated achromatopsia and which is highly unlikely to emerge by chance. Importantly, this change was paired with a significant improvement in psychophysical measures of cone-mediated visual function. These improvements were specific to the treated eye, and provide strong evidence for successful read-out and use of new cone-mediated information. These data show for the first time that gene replacement therapy in achromatopsia within the plastic period of development can awaken dormant cone-signalling pathways after years of deprivation. This reveals unprecedented neural plasticity in the developing human nervous system and offers great promise for emerging regenerative therapies.

Root cause analysis and solution to the degradation of wavelength division multiplexing (WDM) couplers in high power fiber amplifier system.

In the evaluation a fused biconical taper 1480/1580 nm WDM's ability to handle high power cascaded Raman laser throughput (>100 W) a significant degradation in performance was observed. A systematic root cause investigation was conducted and it is experimentally confirmed that the WDM degradation was caused by an interaction between the high power 1480 nm line, an out-of-band Stokes line, and the -OH content of the glass optical fiber. Slanted fiber Bragg grating (SFBG) was introduced to filter out the 1390 nm out-of-band Stokes line in an attempt to avoid this interaction. Ultimately a series of tests were conducted and it was confirmed that the addition of a 1390 nm SFBG in between a high power Raman laser and the high power WDM has successfully prevented the degradation which therefore allowed the continued high power operation of the WDM. NAVAIR Public Release SPR 2013-469 Distribution Statement A-"Approved for Public release; distribution is unlimited".