Geoffrey Arden a,*, Janet Wolf a, Thomas Berninger b, Christopher R. Hogg c, Radouill Tzekov a, Graham E. Holder c a Centre for Applied Vision Research,  epartment of Optometry and Visual Science, City Uni!ersity, 311 -321 Goswell Road, London EC1V 7DD, UK b Eye Hospital, Mathildenstrasse, Munich, Germany c Electrodiagnostic Department, Moorfields Eye Hospital, City Road, London EC1V 2DD, UK Received 12 May 1997; received in revised form 3 October 1997; accepted 20 May 1998
Abstract
Purpose: to measure changes in the relative spectral sensitivities of the dark adapted and light adapted ERG and thus to establish the possible contribution of rods to the ‘blue cone’ ERG elicited by flashes of blue light. Background: short wavelength stimuli in the light-adapted eye evoke small rounded b-waves which have been considered to be S-cone responses. We have recorded such responses from tritanopes, which called the assumptions into question. Methods: small ERGs were recorded to blue and green flashes. The stimulus was a Ganzfeld which employed light emitting diodes. ERGs were obtained in both the dark-adapted eye and after light adaptation to intense orange light (peak wavelength 610 nm). The change in sensitivity with light adaptation and the relative spectral sensitivity was determined from the voltage/log light intensity functions, using a 10 !V criterion. Results: (1) peak times and changes in sensitivity did not help distinguish light-adapted rod from possible S-cone responses; (2) analysis of the change in the ratio of blue:green sensitivity from darkness to 4.4 log Td. 610 nm background suggests that in seven normal subjects, 90% or more of the ERG evoked by 440 nm flashes is generated by S-cones; (3) three tritanopes have insignificantly reduced S-cone responses. Conclusions: (1) clinical techniques used to isolate S-cone ERGs are appropriate; (2) there are at least two types of tritanope and in those we investigated, functional S-cones are probably displaced into the retinal periphery. © 1998 Elsevier Science Ltd. All rights reserved. Keywords: ERG; S-cone; Tritanopia

Yuxin Zhang1,2, Wen-Tao Deng1, Wei Du1,7, Ping Zhu1, Jie Li1, Fan Xu1,3, Jingfen Sun1,8, Cecilia D. Gerstner4, Wolfgang Baehr4, Sanford L. Boye1, Chen  hao2,5, William W. Hauswirth1 & Ji-jing Pang1,2,6
Abstract
Cones are responsible for daylight, central, high acuity and color vision. Three proteins found in human cones, i.e. long-wavelength (L)-, middle-wavelength (M)-,  nd short-wavelength sensitive (S)-opsins, are responsible for red, green and blue color recognition, respectively. Human blue cone monochromacy (BCM) is  haracterized by functional loss of both L- and M-cone opsins due to mutations in the OPN1LW/ OPN1MW gene cluster on the X chromosome. BCM patients, who rely on their vision from only S-cones and rods, suffer severely reduced visual acuity and impaired color vision. Recent studies show that there is sufficient cone  tructure remaining in the central fovea of BCM patients to consider AAV-mediated gene augmentation therapy. In contrast, mouse retina has only two opsins, S-opsin and M-opsin, but no L-opsin. We generated an M-opsin knockout mouse (Opn1mw−/−) expressing only S-opsin as a model for human BCM. We show that recombinant M-opsin delivered by AAV5 vectors rescues M-cone function in Opn1mw−/− mice. We also show that AAV delivered M-opsin localizes in the dorsal cone outer segments, and co-localizes with S-opsin in the ventral retina. Our study demonstrates that cones without M-opsin remain viable and respond to gene augmentation