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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., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Equine recurrent uveitis (ERU) is an ocular inflammatory disease that can be difficult to manage clinically. As such, it is the leading cause of bilateral blindness for horses. ERU is suspected to have a complex autoimmune etiology with both environmental and genetic risk factors contributing to onset and disease progression in some or all cases. Work in recent years has aimed at unraveling the primary triggers, such as infectious agents and inherited breed-specific risk factors, for disease onset, persistence, and progression. This review has aimed at encompassing those factors that have been associated, implicated, or substantiated as contributors to ERU, as well as identifying areas for which additional knowledge is needed to better understand risk for disease onset and progression. A greater understanding of the risk factors for ERU will enable earlier detection and better prognosis through prevention and new therapeutics., (© 2022 American College of Veterinary Ophthalmologists.)

Objective: To characterize clinical manifestations, measure frequency, and evaluate risk factors for equine recurrent uveitis (ERU) in Appaloosa horses in western Canada., Animals: 145 Appaloosa horses., Procedures: Ophthalmic examinations were completed and eyes were classified as having no or mild clinical signs, or moderate, or severe damage from ERU. Clinical signs, age, sex, base coat color, and pattern were recorded. Whole blood and/or mane hair follicles were collected for DNA extraction, and all horses were tested for the leopard complex (LP) spotting pattern allele. Pedigree analysis was completed on affected and unaffected horses, and coefficients of coancestry (CC) and inbreeding (COI) were determined., Results: Equine recurrent uveitis was confirmed in 20 (14%) horses. The mean age of affected horses was 12.3 years (±5.3; range 3-25). Age was a significant risk factor for ERU diagnosis (OR year  = 1.15) and classification (OR year  = 1.19). The fewspot coat pattern was significantly associated with increased risk for ERU compared to horses that were minimally patterned or true solids. The LP/LP genotype was at a significantly greater risk for ERU compared to lp/lp (OR = 19.4) and LP/lp (OR = 6.37). Classification of ERU was greater in the LP/LP genotype compared to LP/lp. Affected horses had an average CC of 0.066, and there was a significant difference in the distribution of CC for affected horses versus the control group (P = .021). One affected horse was the sire or grandsire of nine other affected., Conclusions: Age, coat pattern, and genetics are major risk factors for the diagnosis and classification of ERU in the Appaloosa., (© 2020 American College of Veterinary Ophthalmologists.)

Equine recurrent uveitis (ERU) is an immune-mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T-cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T-cell phenotype. Adipose-derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4 + T-cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T-cells and B-cells in horses with ERU were similar to normal horses. However, CD4 + T-cells from horses with ERU expressed higher amounts of IFNγ indicating a pro-inflammatory Th1 phenotype. When co-incubated with MSCs, activated CD4 + T-cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell-cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4 + T-cell activation phenotype through a combination of cell-cell contact and prostaglandin signaling., (© 2019 The Authors. Veterinary Ophthalmology published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Ophthalmologists.)

Objective: To document a case of limbal squamous cell carcinoma (SCC) in a Rocky Mountain Horse stallion determined to be homozygous for the genetic risk factor (DDB2 c.1013C>T) strongly associated with the disease in Haflinger and Belgian horses, and to determine the frequency of this allele in a larger population of Rocky Mountain Horses., Animals Studied: One privately owned Rocky Mountain Horse and 84 Rocky Mountain Horses screened for allelic frequency., Procedures: A complete ophthalmic examination was performed on a Rocky Mountain Horse stallion for assessment of a mass affecting the right eye. A clinical diagnosis of suspected limbal SCC was made, and routine keratoconjunctivectomy and adjunctive strontium irradiation were performed. Genotyping for the DDB2 c.1013C > T (rs1139682898) risk variant was performed utilizing an allele-specific PCR assay on DNA isolated from whole blood and hair follicles., Results: Histopathology confirmed the limbal mass to be consistent with SCC. The horse was genotyped as homozygous for the DDB2 c.1013C >T risk variant. The frequency of the variant allele among a population of 84 Rocky Mountain Horses was found to be 0.20., Conclusion: The Rocky Mountain Horse breed possesses the DDB2 variant allele determined to be a significant risk factor for ocular SCC in the Haflinger and Belgian breeds. Genotyping additional Rocky Mountain Horses diagnosed with ocular SCC as well as confirmed healthy controls for this variant should be undertaken to determine whether a significant association exists between ocular SCC and the variant in the Rocky Mountain Horse breed., (© 2018 American College of Veterinary Ophthalmologists.)

Objective: To describe the prevalence of LSCC in Haflinger horses and to analyze affected horses' pedigrees investigating the genetic mode of inheritance., Animals: Fifteen horses met inclusion criterion of (i) being of the Haflinger breed, as confirmed by North American Haflinger Registry pedigree and (ii) being diagnosed with LSCC, as confirmed by clinical examination by a veterinary ophthalmologist or by histopathology. Pedigrees could not be obtained for four additional horses diagnosed with LSCC that had been identified as Haflingers., Procedure: Retrospective medical record review of all 19 horses was used to determine patient sex and age at diagnosis. The four-generation pedigrees available for 15 of the horses were used to perform pedigree analysis., Results: Average age of 19 Haflingers at diagnosis with LSCC was 8.7 years. Eleven were males and eight were females. Thirteen of 15 affected horses for whom pedigrees were available shared a common ancestor within five generations, and all 15 shared a common ancestor from the A stallion line in the breed pedigree. Pedigree analysis identified a common sire of two of the affected male horses. Clinical examination of this sire that had no history of LSCC showed no current clinical signs of LSCC, suggesting an autosomal recessive mode of inheritance., Conclusions: Haflingers may be over-represented amongst horses with LSCC and may be diagnosed at a younger age than other breeds. Affected Haflingers appear closely related, suggesting a possible heritable basis for LSCC. The genetic basis for LSCC will be investigated further by a GWAS approach., (© 2014 American College of Veterinary Ophthalmologists.)

Objective:   To determine if congenital stationary night blindness (CSNB) exists in the Miniature Horse in association with leopard complex spotting patterns (LP), and to investigate if CSNB in the Miniature Horse is associated with three single nucleotide polymorphisms (SNPs) in the region of TRPM1 that are highly associated with CSNB and LP in Appaloosas., Animals Studied:   Three groups of Miniature Horses were studied based on coat patterns suggestive of LP/LP (n=3), LP/lp (n=4), and lp/lp genotype (n=4)., Procedures:   Horses were categorized based on phenotype as well as pedigree analysis as LP/LP, LP/lp, and lp/lp. Neurophthalmic examination, slit-lamp biomicroscopy, indirect ophthalmoscopy, and scotopic flash electroretinography were performed on all horses. Hair samples were processed for DNA analysis. Three SNPs identified and associated with LP and CSNB in the Appaloosa were investigated for association with LP and CSNB in these Miniature Horses., Results:   All horses in the LP/LP group were affected by CSNB, while none in the LP/lp or lp/lp groups were affected. All three SNPs were completely associated with LP genotype (χ(2) = 22, P << 0.0005) and CSNB status (χ(2) =11, P<0.0005)., Conclusions:   The Miniature Horse breed is affected by CSNB and it appears to be associated with LP as in the Appaloosa breed. The SNPs tested could be used as a DNA test for CSNB until the causative mutation is determined., (© 2011 American College of Veterinary Ophthalmologists.)