Screen interaction behavior in companion dogs: results from a dog owner survey.

Despite availability of video content marketed for dog (Canis familiaris) entertainment, there is little information on dog behaviors when viewing content, nor describing which content is engaging. The aims of this study were to define demographics of dogs that engage with screens, owner observed behaviors, and perceived content interest. A digital survey was distributed to dog owners (03/2022-03/2023). We collected demographics, home environment, owner-rated behaviors, content interest, and interest in 4 presented videos. We compared the representation of dogs from different purebred dog groups (categorized by job/purpose by the American Kennel Club) with the estimated general purebred dog population. Most respondents (total n=1,246) lived in the USA (89%). Median age was 4 years, 54% were purebred, 51% were female. Most (86%, n=1,077) stated their dog watched screen content. Excitement behaviors were often described: 78% of dogs approached the screen, 76% vocalized. Many owners played videos for their dogs when left alone. Dogs most frequently engaged with animal content; dogs were the most popular animal. Age and visual status influenced the frequency of perceived interaction; age and breed influenced content interest. Within purebred dogs that were stated to watch content, there was a relative over-representation of "sporting" and "herding"-type breeds. A dog's age, visual status, and breed type may influence their interest in video content at home. Because many owners reported excitement in their dogs in reaction to screen content, owners may wish to determine whether video content would be suitable for use when their dogs are left alone.

A modified silent substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs.

OBJECTIVE: A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using silent substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED: Three normal adult purpose-bred beagles (2 females and 1 male). METHODS: Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS: In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P < .001). CONCLUSION: We present a clinically applicable method to consistently isolate rod and cone subclass function in sedated dogs. This may allow detailed evaluation of photoreceptor function in clinical patients with rod or cone subclass deficits without the need for general anesthesia or protracted adaptation times.

Differential targeting of feline photoreceptors by recombinant adeno-associated viral vectors: implications for preclinical gene therapy trials.

The cat is emerging as a promising large animal model for preclinical testing of retinal dystrophy therapies, for example, by gene therapy. However, there is a paucity of studies investigating viral vector gene transfer to the feline retina. We therefore sought to study the tropism of recombinant adeno-associated viral (rAAV) vectors for the feline outer retina. We delivered four rAAV serotypes: rAAV2/2, rAAV2/5, rAAV2/8 and rAAV2/9, each expressing green fluorescent protein (GFP) under the control of a cytomegalovirus promoter, to the subretinal space in cats and, for comparison, mice. Cats were monitored for gene expression by in vivo imaging and cellular tropism was determined using immunohistochemistry. In cats, rAAV2/2, rAAV2/8 and rAAV2/9 vectors induced faster and stronger GFP expression than rAAV2/5 and all vectors transduced the retinal pigment epithelium (RPE) and photoreceptors. Unlike in mice, cone photoreceptors in the cat retina were more efficiently transduced than rod photoreceptors. In mice, rAAV2/2 only transduced the RPE whereas the other vectors also transduced rods and cones. These results highlight species differences in cellular tropism of rAAV vectors in the outer retina. We conclude that rAAV serotypes are suitable for use for retinal gene therapy in feline models, particularly when cone photoreceptors are the target cell.

Tyrosine capsid-mutant AAV vectors for gene delivery to the canine retina from a subretinal or intravitreal approach.

Recombinant adeno-associated viruses are important vectors for retinal gene delivery. Currently utilized vectors have relatively slow onset, and for efficient transduction it is necessary to deliver treatment subretinally, with the potential for damage to the retina. Amino-acid substitutions in the viral capsid improve efficiency in rodent eyes by evading host responses. As dogs are important large animal models for human retinitis pigmentosa, we evaluated the speed and efficiency of retinal transduction using capsid-mutant vectors injected both subretinally and intravitreally. We evaluated AAV serotypes 2 and 8 with amino-acid substitutions of surface-exposed capsid tyrosine residues. The chicken beta-actin promoter was used to drive green fluorescent protein expression. Twelve normal adult beagles were injected; four dogs received intravitreal injections and eight dogs received subretinal injections. Capsid-mutant viruses tested included AAV2(quad Y-F) (intravitreal and subretinal) and self-complementary scAAV8(Y733F) (subretinal only). Contralateral control eyes received injections of scAAV5 (subretinal) or scAAV2 (intravitreal). Subretinally delivered vectors had a faster expression onset than intravitreally delivered vectors. Subretinally delivered scAAV8(Y733F) had a faster onset of expression than scAAV5. All subretinally injected vector types transduced the outer retina with high efficiency and the inner retina with moderate efficiency. Intravitreally delivered AAV2(quad Y-F) had a marginally higher efficiency of transduction of both outer retinal and inner retinal cells than scAAV2. Because of their rapid expression onset and efficient transduction, subretinally delivered capsid-mutant AAV8 vectors may increase the efficacy of gene therapy treatment for rapid photoreceptor degenerative diseases. With further refinement, capsid-mutant AAV2 vectors show promise for retinal gene delivery from an intravitreal approach.

RPE65 gene therapy slows cone loss in Rpe65-deficient dogs.

Recent clinical trials of retinal pigment epithelium gene (RPE65) supplementation therapy in Leber congenital amaurosis type 2 patients have demonstrated improvements in rod and cone function, but it may be some years before the effects of therapy on photoreceptor survival become apparent. The Rpe65-deficient dog is a very useful pre-clinical model in which to test efficacy of therapies, because the dog has a retina with a high degree of similarity to that of humans. In this study, we evaluated the effect of RPE65 gene therapy on photoreceptor survival in order to predict the potential benefit and limitations of therapy in patients. We examined the retinas of Rpe65-deficient dogs after RPE65 gene therapy to evaluate the preservation of rods and cone photoreceptor subtypes. We found that gene therapy preserves both rods and cones. While the moderate loss of rods in the Rpe65-deficient dog retina is slowed by gene therapy, S-cones are lost extensively and gene therapy can prevent that loss, although only within the treated area. Although LM-cones are not lost extensively, cone opsin mislocalization indicates that they are stressed, and this can be partially reversed by gene therapy. Our results suggest that gene therapy may be able to slow cone degeneration in patients if intervention is sufficiently early and also that it is probably important to treat the macula in order to preserve central function.