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Originally published In Press as doi:10.1167/iovs.07-1159 on January 25, 2008
(Investigative Ophthalmology and Visual Science. 2008;49:2208-2215.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1159

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Multifocal Electroretinogram in Rhodopsin P347L Transgenic Pigs

Yiu-fai Ng,1 Henry H. L. Chan,1 Patrick H. W. Chu,1 Chi-ho To,1 Brian C. Gilger,2 Robert M. Petters,3 and Fulton Wong4,5

1From the Laboratory of Experimental Optometry (Neuroscience), School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR, China; the 2Department of Clinical Sciences, College of Veterinary Medicine, and the 3Department of Animal Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina; and the 4Departments of Ophthalmology and 5Neurobiology, School of Medicine, Duke University, Durham, North Carolina.

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.








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