@article{sommer_wong_petters_2011, title={Phenotypic stability of Pro347Leu rhodopsin transgenic pigs as indicated by photoreceptor cell degeneration}, volume={20}, ISSN={["0962-8819"]}, DOI={10.1007/s11248-011-9491-0}, abstractNote={Rhodopsin (Pro347Leu) transgenic pigs are recognized to be an excellent model for the human disease, retinitis pigmentosa. First published in 1997, the rhodopsin transgenic pigs have been maintained since that time at North Carolina State University by outcrossing hemizygous boars to unrelated sows. Nine generations of outcrossing have been completed. Since the genetic background of these pigs has undoubtedly changed, the question of the current phenotype of the transgenic pigs is relevant for their future use. Age-matched transgenic and non-transgenic eyes were submitted for histological analysis using hematoxylin and eosin staining. Even by 2 weeks of age, significant thinning of the outer nuclear layer of photoreceptors was observed. For ages 3 and 4 weeks, thinning was noted similar to that of 2 weeks of age. By 6 weeks of age outer nuclear layer thinning was greater than that of earlier age. At 11 weeks of age, most of the rods have degenerated leaving only a few layers of cones. In all, the phenotype, based on assessment of photoreceptor degeneration, is similar to that of the first description of the transgenic animals. As such the Pro347Leu rhodopsin transgenic pigs have exhibited phenotypic stability through generations of outcrossing and can be used confidently in future studies of the type of retinal degeneration seen with retinitis pigmentosa.}, number={6}, journal={TRANSGENIC RESEARCH}, author={Sommer, Jeffrey R. and Wong, Fulton and Petters, Robert M.}, year={2011}, month={Dec}, pages={1391–1395} }
 @article{ng_chan_chu_to_gilger_petters_wong_2008, title={Multifocal Electroretinogram in Rhodopsin P347L Transgenic Pigs}, volume={49}, ISSN={1552-5783}, url={http://dx.doi.org/10.1167/iovs.07-1159}, DOI={10.1167/iovs.07-1159}, abstractNote={PURPOSE
Neural ectopic rewiring in retinal degeneration such as retinitis pigmentosa (RP) may form functional synapses between cones and rod bipolar cells that cause atypical signal processing. In this study, the multifocal electroretinograms (mfERGs) of a large animal model of RP, the rhodopsin P347L transgenic (Tg) pig, were measured to examine the sources and nature of altered signal processing.


METHODS
mfERG responses from a 6-week-old Tg pig were recorded before and after sequential application of tetrodotoxin (TTX), N-methyl-D-aspartate (NMDA), 2-amino-4-phosphonobutyric acid (APB), and cis-2,3-piperidinedicarboylic acid (PDA), to identify contributions to the retinal signal from inner retinal neurons, the ON-pathway, the OFF-pathway, and photoreceptors. The mfERG response contributions from different retinal components of in the Tg eyes were estimated and compared with control data from eyes of age-matched wild-type (WT) pigs.


RESULTS
There was a prominent difference in the estimates of the inner retinal response and ON-bipolar cell pathway contribution between the Tg and WT mfERG responses. In particular, the early components of the inner retinal contribution were obviously altered in the Tg mfERG. The inner retinal components at approximately 24 and 40 ms appeared to be inverted. Differences in the estimates of OFF-bipolar cell pathway contributions were minimal. There was no change in cone cell responses in the Tg mfERG.


CONCLUSIONS
In Tg retinas, ectopic synapses formed between cones and rod bipolar cells probably altered signal processing of the ON-bipolar cell pathway. In response to the altered visual signal input from the outer retina, signal processing in inner retinal neurons was also modified.}, number={5}, journal={Investigative Opthalmology & Visual Science}, publisher={Association for Research in Vision and Ophthalmology (ARVO)}, author={Ng, Yiu-fai and Chan, Henry H. L. and Chu, Patrick H. W. and To, Chi-ho and Gilger, Brian C. and Petters, Robert M. and Wong, Fulton}, year={2008}, month={May}, pages={2208} }
 @article{chu_chan_ng_brown_siu_beale_gilger_wong_2008, title={Porcine global flash multifocal electroretinogram: Possible mechanisms for the glaucomatous changes in contrast response function}, volume={48}, ISSN={0042-6989}, url={http://dx.doi.org/10.1016/j.visres.2008.05.006}, DOI={10.1016/j.visres.2008.05.006}, abstractNote={The aim of this study was to obtain a better understanding of the cellular contributions to the porcine global flash mfERG by using a pharmacologic dissection method, together with the method using variation of stimulus contrast which has been used to demonstrate mfERG changes in human glaucoma.Global flash mfERGs with different stimulus-contrast settings (99%, 65%, 49% or 29%) were recorded from 14 eyes of ten 6-week-old Yorkshire pigs in control conditions and after suppression of inner retinal responses with inhalation of isoflurance (ISO), and injections of tetrodotoxin (TTX) and N-methyl-d-aspartic acid (NMDA). ON- and OFF-pathway responses were isolated by injection of 2-amino-4-phosphonobutyric acid (APB) and cis-2,3-piperidinedicarboylic acid (PDA).The porcine global flash mfERG consisted of an early direct component (DC) and a late induced component (IC). ISO and TTX removed inner retinal contributions to the IC; NMDA application further abolished the oscillatory wavelets in the DC and removed the residual IC waveform. The inner retina contributed regular oscillation-like wavelets (W1, W2 and W3) to the DC and shaped the IC. After removing the inner retinal contributions, the porcine global flash mfERG waveform becomes comparable to that obtained with conventional mfERG stimulation. The remaining waveform (smoothed DC) was mainly contributed by the ON- and OFF-bipolar cells as revealed after APB or PDA injection. Photoreceptors contributed a small signal to the leading edge of N1. The characteristic of contrast response function of DC was demonstrated to be contributed by the inner retinal oscillation-like wavelets.We believe that the DC of the porcine global flash mfERG is mainly composed of contributions from photoreceptors, and ON- and OFF-bipolar cells, where inner retinal activity partially shaped the DC with superimposed regular wavelets. However, the IC is dominated by inner retinal activity. The contrast response functions of DC consisted of both outer retinal response and oscillation-like wavelets of the inner retinal response. Both contain different characteristics during contrast modulation of the stimulus, where the changes of W2 of the inner retinal response seem independent of contrast modulation. The DC contrast response feature depends mainly on the relative contribution of inner retinal activities; the loss of inner retinal cells may alter the DC contrast response function, making it tend toward linearity.}, number={16}, journal={Vision Research}, publisher={Elsevier BV}, author={Chu, Patrick H.W. and Chan, Henry H.L. and Ng, Yiu-fai and Brown, Brian and Siu, Andrew W. and Beale, Brady A. and Gilger, Brian C. and Wong, Fulton}, year={2008}, month={Jul}, pages={1726–1734} }