A Novel Method for Objective Vision Testing in Canine Models of Inherited Retinal Disease

Gearhart, Patricia M.; Gearhart, Chris; Petersen‐Jones, Simon M.

doi:10.1167/iovs.07-0625

Cited by 31 publications

(38 citation statements)

References 26 publications

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“…31 Visual function was evaluated at normal room light and two lower light intensities, by recording the time to exit the device and the first exit tunnel entered. A significant improvement in visual function relative to pre-treatment values was seen at the two lower light intensities for both parameters evaluated ( Figure 5).…”

Section: Evaluation Of Visionmentioning

confidence: 99%

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Gene therapy in the second eye of RPE65-deficient dogs improves retinal function

Annear

Bartoe

Barker³

et al. 2010

Gene Ther

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The purpose of this study was to evaluate whether immune responses interfered with gene therapy rescue using subretinally delivered recombinant adeno-associated viral vector serotype 2 carrying the RPE65 cDNA gene driven by the human RPE65 promoter (rAAV2.hRPE65p.hRPE65) in the second eye of RPE65À/À dogs that had previously been treated in a similar manner in the other eye. Bilateral subretinal injection was performed in nine dogs with the second eye treated 85-180 days after the first. Electroretinography (ERG) and vision testing showed rescue in 16 of 18 treated eyes, with no significant difference between first and second treated eyes. A serum neutralizing antibody (NAb) response to rAAV2 was detected in all treated animals, but this did not prevent or reduce the effectiveness of rescue in the second treated eye. We conclude that successful rescue using subretinal rAAV2.hRPE65p.hRPE65 gene therapy in the second eye is not precluded by prior gene therapy in the contralateral eye of the RPE65À/À dog. This finding has important implications for the treatment of human LCA type II patients. Gene Therapy (2011) The condition is characterized by severe visual impairment in dim light, typically progressing to complete blindness in the second decade of life. LCA type II results from mutations in the RPE65 gene, and accounts for 10-15% of LCA cases. 2,3 RPE65 encodes a protein that forms an essential component of the visual cycle and is expressed within the retinal pigment epithelium. 3 The visual cycle is responsible for the supply of the chromophore, 11-cis-retinal, to the photoreceptor cells for combination with the rod and cone opsins to form the visual pigments. RPE65 is an isomerohydrolase that converts esters of vitamin A to 11-cis-retinol for subsequent oxidation to 11-cis-retinal prior to transport to the photoreceptors. A spontaneous 4 basepair deletion in RPE65 in the Briard breed of dog results in a premature stop codon and an absence of RPE65 gene product, resulting in a very similar phenotype to LCA type II. 4 Affected dogs have markedly reduced vision and an abnormal electroretinogram with greatly elevated threshold of responses. 4,5 The similarities between the human and canine disease resulting from RPE65 mutations, make the RPE65À/À Briard a valuable large animal model for LCA type II.Dramatic restoration of vision with gene therapy was first reported in the canine RPE65À/À model of LCA. 6 A number of studies have shown rod and cone photoreceptor rescue using rAAV vectors to deliver a normal copy of the RPE65 gene via a subretinal injection in the RPE65 mutant Briard. [6][7][8][9][10][11][12][13] On the basis of the great success of the canine trials, phase I/II clinical trials of rAAV-RPE65 gene replacement therapy in human LCA patients have started with the first reported results showing great promise. 14-16 Thus far in all human patients only one eye has been treated. A critical aspect of the management of LCA

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Section: Evaluation Of Visionmentioning

confidence: 99%

“…31 Evaluation was performed twice, before injection and 70-255 days post-injection for all dogs. Each injected eye was individually assessed by placement of an eye mask over the contralateral eye.…”

Section: Vision Testingmentioning

confidence: 99%

Gene therapy in the second eye of RPE65-deficient dogs improves retinal function

Annear

Bartoe

Barker³

et al. 2010

Gene Ther

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“…Os procedimentos mais comumente utilizados para análise da visão durante a rotina clínica oftálmica são aqueles que testam a capacidade da retina para detectar movimentos, como resposta de ameaça e capacidade para seguir um algodão (OFFRI, 1999) ou testes comportamentais caracterizados pela tomada de decisão pelo animal, baseada em indícios visuais (GEARHART et al, 2008). Nossos resultados contribuem para a normatização de um exame objetivo, o PVE-PR com tabuleiro de xadrez em gatos adultos sem o uso de midriáticos e sedativos.…”

Section: Discussionunclassified

“…Os testes visuais nos animais podem ser realizados de várias maneiras, como métodos comportamentais (MILLER & MURPHY, 1995;GEARHART et al, 2008), discriminação de formas e aprendizagens (TANAKA, 2000), nistagmo optocinético (EZHE et al, 1990), eletrorretinograma (ERG) (ROSOLEN et al, 2005) e potencial visual evocado (PVE) (MURPHY et al, 1997).…”

Section: Introductionunclassified

Potencial visual evocado por padrão reverso com tabuleiro de xadrez em gatos domésticos adultos

et al. 2015

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RESUMO O potencial visual evocado por padrão reverso (PVE-PR) é um método objetivo, não invasivo e estabelecido para as investigações funcionais. Este trabalho teve como objetivo a obtenção de dados do PVE-PR com tabuleiro de xadrez em gatos (16', 32', 64', 130' e 260'de arco Palavras-chave: felinos, teste eletrofisiológico, oftalmologia. ABSTRACT The pattern reversal visual evoked potential (PR-VEP) is an objective method, stablished for noninvasive functional investigations. This research aimed to obtain data from the PR-VEP with checkerboard in adult domestic cats and the influence of different visual angles on the peak latency and implicit time ofwaves N75 and P100. It was used 13 adult cats (2-4 years old), of both sexes. Each animal was positioned 100 cm away from a video monitor located at 17.2º. The stimulus generated for the formation of wave VEPs was "square" with the frequency of 6Hz, presented in five spatial frequencies (16 ', 32', 64 ', 130' and 260 'of arc). Mean values of implicit times (ms) and amplitudes (µvolts) of P100were not statistically different and were not correlated (r=0.067

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“…27 An elegant vision testing apparatus has been described for objective assessment of navigational vision in dogs. 29 The device consists of a junction box with 4 exit tunnels. The dogs are placed in the junction box and given 1 vision-based choice for exit.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a behavioral method for objective vision testing and identification of achromatopsia in dogs

Garcia¹,

Ying²,

Cocores³

et al. 2010

Journal of the American Veterinary Medical Association

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Objective-To develop a quantifiable behavioral test for identification of achromatopsic dogs based on visual performance. Animals-14 dogs.Procedures-A 3.6-m-long obstacle-avoidance course with 6 obstacle panels was developed from a preliminary 2.4-m-long course. Achromatopsic and visually normal control dogs were run through the course at 4 ambient light intensities (from dim to bright: 0.2, 25, 65, and 646 lux). Completion of 4 runs ranging from dimmest to brightest light intensity constituted 1 complete trial. Each dog underwent 3 trials. Transit times were measured and compared between dog groups and between light intensities by use of a generalized linear model and ANOVA.Results-At the 3 highest light intensities, the achromatopsic dogs needed significantly more time to pass through the obstacle course than the control animals. Compared with the mean transit time at the lowest light intensity, mean transit times were 2.6 times as long at 25 lux, 3.2 times as long at 65 lux, and 5.7 times as long at 646 lux. The achromatopsic dogs had signs of increasing difficulty navigating around the obstacle panels with increasing light intensities; this was not the situation for the control dogs. Conclusions and ClinicalRelevance-A 3.6-m-long obstacle-avoidance course with 6 movable obstacle panels allowed identification of achromatopsic dogs at ambient light intensities ≥ 25 lux based on transit times. This test could be helpful in the evaluation of new cone photoreceptorspecific treatments.The clinical, psychophysical evaluation of visual performance is generally less sophisticated in because of limitations in the assessment of responses to visual stimuli by an untrained animal. The testing of general visual performance in dogs is usually limited to rather simple methods such as the menace response test, the visual placing reaction, and the tracking of objects such as a cotton ball or laser pointer. 1,2 In a clinical setting, dogs may be observed maneuvering around obstacles under different, often ill-defined, ambient light intensities in the examination

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A Novel Method for Objective Vision Testing in Canine Models of Inherited Retinal Disease

Cited by 31 publications

References 26 publications

Gene therapy in the second eye of RPE65-deficient dogs improves retinal function

Gene therapy in the second eye of RPE65-deficient dogs improves retinal function

Potencial visual evocado por padrão reverso com tabuleiro de xadrez em gatos domésticos adultos

Evaluation of a behavioral method for objective vision testing and identification of achromatopsia in dogs

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