Enhancement of ON-Bipolar Cell Responses of Cone Electroretinograms in Rabbits with the Pro347Leu Rhodopsin Mutation

Abstract

A depolarizing pattern of the cone ERG responses was seen in Pro347Leu Tg rabbits. The enhancement or preservation of the ON-bipolar cell response in the ERGs contributed to shaping the waveform in the Tg rabbits. In this model, the functional alterations in the ON-pathway took place before the deterioration of cone photoreceptor function.

Photoreceptor and Post-Photoreceptoral Contributions to Photopic ERG a-Wave in Rhodopsin P347L Transgenic Rabbits

“…Similarly, detailed ERG studies in rhodopsin P347L Tg pigs and rabbits have demonstrated that the electrical activities of the cone ON-pathway were also enhanced at a relatively early stage of retinal degeneration. 18,23 In addition, an increase in the ERG responses from the inner retina (e.g., scotopic threshold response) was also reported in the retina of the aged Royal College of Surgeons rat, a rodent model of retinal degeneration. 24,25 Taken together, inherited retinal diseases associated with progressive photoreceptor degeneration may lead to different types of functional changes in the post-photoreceptoral retinal circuits, including the ON-and OFF pathways, during a relatively early stage of retinal degeneration.…”

“…15,16,18 The drugs were dissolved in sterile PBS, and the pH was titrated to 7.4 with hydrochloric acid or sodium hydrate. The drugs were injected into the vitreous with a 30-gauge needle inserted through the pars plana approximately 1 mm posterior to the limbus.…”

“…This makes it difficult to quantify the changes in the a-wave amplitude before and after intravitreal injection of pharmacologic agents. 8 -12 We have recently succeeded in generating a rabbit model of retinal degeneration.13 This animal has the rhodopsin Pro347Leu mutation, which is one of the major mutations in autosomal dominant retinitis pigmentosa in humans.14 These animals have a slowly progressive photoreceptor degeneration, as do human RP patients with this mutation, 13,[15][16][17][18] though it is still unclear whether the retinal degeneration is due to a point mutation of the rhodopsin gene or to an overexpression of rhodopsin in these animals. We believed that this rhodopsin transgenic (Tg) rabbit can be an excellent animal model in which to study the retinal origins of the photopic ERG a-wave in RP because rabbits have a large photopic a-wave.…”

“…In addition, the large size of the rabbit's eye enabled us to perform reliable intravitreal injections of pharmacologic agents. 15,16,18 Thus, the purpose of this study was to compare the contributions of cone photoreceptors and post-photoreceptoral neurons with the a-wave of the photopic ERGs between wild-type (WT) and Tg rabbits. To accomplish this we examined the postphotoreceptoral neural activity before and after they were blocked by pharmacologic agents.…”

Contributions of Second- and Third-Order Retinal Neurons to Cone Electroretinograms After Loss of Rod Function in Rhodopsin P347L Transgenic Rabbits

“…Interestingly, several ERG studies using pharmacologic dissection of the retinal circuits in this model revealed an Copyright 2017 The Authors iovs.arvojournals.org j ISSN: 1552-5783 enhancement of the function of the second-or third-order retinal neurons. [16][17][18] This rabbit model of RP has at least two benefits in ERG analyses compared with the rodent models of eyes with RP. The first is that rabbits have large eyes, which allowed us to perform multiple intravitreal injections of different agents.…”