Generation of a Transgenic Rabbit Model of Retinal Degeneration

2009 ◽  
Vol 50 (3) ◽  
pp. 1371 ◽  
Author(s):  
Mineo Kondo ◽  
Takao Sakai ◽  
Keiichi Komeima ◽  
Yukihide Kurimoto ◽  
Shinji Ueno ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Rabbit Model ◽  
Transgenic Rabbit

scholarly journals Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

2020 ◽  
Vol 21 (3) ◽  
pp. 704 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Viktoriia E. Baksheeva ◽  
Veronika V. Tiulina ◽  
Sergei V. Goriainov ◽  
Nadezhda V. Azbukina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Aqueous Humor ◽  
Rabbit Model ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Cyclooxygenase Inhibitor ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.

Supernormal ERG Oscillatory Potentials in Transgenic Rabbit with Rhodopsin P347L Mutation and Retinal Degeneration

2009 ◽  
Vol 50 (9) ◽  
pp. 4402 ◽  
Author(s):  
Takao Sakai ◽  
Mineo Kondo ◽  
Shinji Ueno ◽  
Toshiyuki Koyasu ◽  
Keiichi Komeima ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Oscillatory Potentials ◽  
Transgenic Rabbit

scholarly journals Pore mutants of HERG and KvLQT1 downregulate the reciprocal currents in stable cell lines

2010 ◽  
Vol 299 (5) ◽  
pp. H1525-H1534 ◽  
Author(s):  
Xiao-Qin Ren ◽  
Gong Xin Liu ◽  
Louise E. Organ-Darling ◽  
Renjian Zheng ◽  
Karim Roder ◽  
...  
Keyword(s):  
Cell Lines ◽  
Rabbit Model ◽  
Chinese Hamster ◽  
Expression Vectors ◽  
Delayed Rectifier ◽  
Wild Type ◽  
Cho Cell ◽  
Surface Plasmon Resonance Analysis ◽  
Transgenic Rabbit

We previously reported a transgenic rabbit model of long QT syndrome based on overexpression of pore mutants of repolarizing K+ channels KvLQT1 (LQT1) and HERG (LQT2).The transgenes in these rabbits eliminated the slow and fast components of the delayed rectifier K+ current ( IKs and IKr, respectively), as expected. Interestingly, the expressed pore mutants of HERG and KvLQT1 downregulated the remaining reciprocal repolarizing currents, IKs and IKr, without affecting the steady-state levels of the native polypeptides. Here, we sought to further explore the functional interactions between HERG and KvLQT1 in heterologous expression systems. Stable Chinese hamster ovary (CHO) cell lines expressing KvLQT1-minK or HERG were transiently transfected with expression vectors coding for mutant or wild-type HERG or KvLQT1. Transiently expressed pore mutant or wild-type KvLQT1 downregulated IKr in HERG stable CHO cell lines by 70% and 44%, respectively. Immunostaining revealed a severalfold lower surface expression of HERG, which could account for the reduction in IKr upon KvLQT1 expression. Deletion of the KvLQT1 NH2-terminus did not abolish the downregulation, suggesting that the interactions between the two channels are mediated through their COOH-termini. Similarly, transiently expressed HERG reduced IKs in KvLQT1-minK stable cells. Coimmunoprecipitations indicated a direct interaction between HERG and KvLQT1, and surface plasmon resonance analysis demonstrated a specific, physical association between the COOH-termini of KvLQT1 and HERG. Here, we present an in vitro model system consistent with the in vivo reciprocal downregulation of repolarizing currents seen in transgenic rabbit models, illustrating the importance of the transfection method when studying heterologous ion channel expression and trafficking. Moreover, our data suggest that interactions between KvLQT1 and HERG are mediated through COOH-termini.

scholarly journals Resolution of Established Cardiac Hypertrophy and Fibrosis and Prevention of Systolic Dysfunction in a Transgenic Rabbit Model of Human Cardiomyopathy Through Thiol-Sensitive Mechanisms

Circulation ◽  
2009 ◽  
Vol 119 (10) ◽  
pp. 1398-1407 ◽  
Author(s):  
Raffaella Lombardi ◽  
Gabriela Rodriguez ◽  
Suet Nee Chen ◽  
Crystal M. Ripplinger ◽  
Wenwen Li ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Systolic Dysfunction ◽  
Rabbit Model ◽  
Transgenic Rabbit

scholarly journals Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with Long-QT syndrome 1 both in vitro and in vivo

2011 ◽  
Vol 650 (1) ◽  
pp. 309-316 ◽  
Author(s):  
Jürgen Biermann ◽  
Kezhong Wu ◽  
Katja E. Odening ◽  
Stefan Asbach ◽  
Gideon Koren ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Long Qt ◽  
Transgenic Rabbit ◽  
Qt Syndrome

scholarly journals Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome

2009 ◽  
Vol 587 (19) ◽  
pp. 4661-4680 ◽  
Author(s):  
Ohad Ziv ◽  
Eduardo Morales ◽  
Yoon-kyu Song ◽  
Xuwen Peng ◽  
Katja E. Odening ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Long Qt ◽  
Complex Behaviour ◽  
Transgenic Rabbit ◽  
Qt Syndrome

scholarly journals TTX Converts Polymorphic VT to Monomorphic VT in Transgenic Rabbit Model of LQT1

2013 ◽  
Vol 104 (2) ◽  
pp. 294a
Author(s):  
Zachary A. Pfeiffer ◽  
Jung Min Hwang ◽  
Brijesh Patel ◽  
Tae Yun Kim ◽  
Xuwen Peng ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Transgenic Rabbit
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