Additional evidence supports GRM6 p.Thr178Met as a cause of congenital stationary night blindness in three horse breeds.

Congenital stationary night blindness (CSNB) is an ocular disorder characterized by nyctalopia. An autosomal recessive missense mutation in glutamate metabotropic receptor 6 (GRM6 c.533C>T, p.(Thr178Met)), called CSNB2, was previously identified in one Tennessee Walking Horse and predicted to reduce binding affinity of the neurotransmitter glutamate, impacting the retinal rod ON-bipolar cell signaling pathway. Thus, the first aim was to identify the allele frequency (AF) of CSNB2 in breeds with reported cases of CSNB and breeds closely related to the Tennessee Walking Horse. The second aim was to perform ocular examinations in multiple breeds to confirm the link between genotype and CSNB phenotype. In evaluating 3518 horses from 14 breeds, the CSNB2 allele was identified in nine previously unreported breeds. The estimated AF was highest in pacing Standardbreds (0.17) and lowest in American Quarter Horses (0.0010). Complete ophthalmic examinations and electroretinograms (ERG) were performed on 19 horses from three breeds, including one CSNB2 homozygote from each breed. All three CSNB2/CSNB2 horses had an electronegative ERG waveform under scotopic light conditions consistent with CSNB. The remaining 16 horses (seven CSNB2/N and nine N/N) had normal scotopic ERG results. All horses had normal photopic ERGs. This study provides additional evidence that GRM6 c.533C>T homozygosity is likely causal to CSNB in Tennessee Walking Horses, Standardbreds, and Missouri Fox Trotting Horses. Genetic testing is recommended for breeds with the CSNB2 allele to limit the production of affected horses. This study represents the largest across-breed identification of CSNB in the horse and suggests that this disorder is likely underdiagnosed.

Long-term results (>1 year) in 19 dogs treated with MicroPulse transscleral diode cyclophotocoagulation for refractory glaucoma.

OBJECTIVE: To report the long-term (>1 year) outcome of MicroPulse transscleral diode cyclophotocoagulation (MP-TSCP) in dogs. ANIMALS STUDIED: Client owned dogs that underwent MP-TSCP at a veterinary referral center. PROCEDURE: Retrospective study of 19 dogs treated with MP-TSCP. Dogs were evaluated at a median follow-up time of 30.5 months postoperatively. Reported outcomes were intraocular pressure (IOP), retention or loss of vision, number of medications, and additional procedures performed. Variables associated with time to treatment failure were evaluated. RESULTS: Data from 19 dogs (24 eyes) was available. Median laser settings employed were 140 s and 2200 mW at 31.3% duty cycle. Long-term postoperative IOP was lower than preoperative IOP values (14 mmHg (IQR = 22 mmHg, range: 4-52 mmHg) versus 30 mmHg (IQR = 31 mmHg, range: 8-62 mmHg), respectively). Laser settings >2000 mW were associated with a significantly longer time to reported failure. MP-TSCP was the sole therapy performed in 16/24 eyes resulting in long-term IOP control in 13/24 eyes and retention of vision in 6 of the 14 sighted eyes. Repeat MP-TSCP was performed in 10/24 eyes. Eight of 24 eyes required additional procedures with long-term IOP control in 4/8 eyes. CONCLUSIONS: MicroPulse transscleral diode cyclophotocoagulation can be an effective treatment for refractory glaucoma in select cases. Higher laser settings increased time to reported failure, whereas age, glaucoma type, and preoperative IOP did not affect survival. MP-TSCP as sole therapy or coupled with additional glaucoma procedures controlled the IOP in 70% of cases.

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases.

Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is a review that highlights current canine models of human diseases, including Alzheimer's disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials.