Corneal epithelial inclusion cysts in 12 dogs (13 eyes) from 2010 to 2019: A multicentric retrospective study.

OBJECTIVE: The aim of this retrospective study was to review the clinical data and outcomes of patients that suffered corneal epithelial inclusion cysts (CEIC). Animals studied Thirteen eyes from 12 dogs from multiple private practices in France and Belgium, with a strong clinical of CEIC were included in the study. RESULTS: The mean age of affected dogs was 9 years. There were 9 females and 3 males. Two out of 12 dogs were Shih Tzus. Where identified, etiology was traumatic. Eleven dogs were affected unilaterally, 1 bilaterally. The cysts were single, bi-lobulated, or tri-lobulate, and cyst size ranged from 1 to 6 mm in diameter. Keratectomy alone was performed in seven cases, in conjunction with a conjunctival graft in three cases, a porcine small intestine mucosa graft in two cases, or an amniotic membrane graft in one case. Histopathologic findings were consistent in all eyes with a cyst located in the corneal stroma, composed of a nonkeratinized squamous epithelium delineating a lumen filled with neutrophils and desquamated epithelial cells. Surgery was curative in all cases but one, where the removal was incomplete and recurrence occurred several weeks after the surgery. CONCLUSION: Corneal epithelial inclusion cysts is a rare condition, secondary to corneal trauma, which can be treated successfully with conventional keratectomy alone or in conjunction with graft procedures.

Natural models for retinitis pigmentosa: progressive retinal atrophy in dog breeds.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders eventually leading to blindness with different ages of onset, progression and severity. Human RP, first characterized by the progressive degeneration of rod photoreceptor cells, shows high genetic heterogeneity with more than 90 genes identified. However, about one-third of patients have no known genetic causes. Interestingly, dogs are also severely affected by similar diseases, called progressive retinal atrophy (PRA). Indeed, RP and PRA have comparable clinical signs, physiopathology and outcomes, similar diagnosis methods and most often, orthologous genes are involved. The many different dog PRAs often segregate in specific breeds. Indeed, undesired alleles have been selected and amplified through drastic selection and excessive use of inbreeding. Out of the 400 breeds, nearly 100 have an inherited form of PRA, which are natural animal models that can be used to investigate the genetics, disease progression and therapies in dogs for the benefit of both dogs and humans. Recent knowledge on the canine genome and access to new genotyping and sequencing technologies now efficiently allows the identification of mutations involved in canine genetic diseases. To date, PRA genes identified in dog breeds correspond to the same genes in humans and represent relevant RP models, and new genes found in dogs represent good candidate for still unknown human RP. We present here a review of the main advantages of the dog models for human RP with the genes already identified and an X-linked PRA in the Border collie as a model for orphan X-linked RPs in human.

A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies.

Human Hereditary Sensory Autonomic Neuropathies (HSANs) are characterized by insensitivity to pain, sometimes combined with self-mutilation. Strikingly, several sporting dog breeds are particularly affected by such neuropathies. Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact. Through a Genome Wide Association Study (GWAS) with 24 affected and 30 unaffected sporting dogs using the Canine HD 170K SNP array (Illumina), we identified a 1.8 Mb homozygous locus on canine chromosome 4 (adj. p-val = 2.5x10-6). Targeted high-throughput sequencing of this locus in 4 affected and 4 unaffected dogs identified 478 variants. Only one variant perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in a long intergenic non-coding RNAs (lincRNA), GDNF-AS. Using human comparative genomic analysis, we observed that the canine variant maps onto an enhancer element. Quantitative RT-PCR of dorsal root ganglia RNAs of affected dogs showed a significant decrease of both GDNF mRNA and GDNF-AS expression levels (respectively 60% and 80%), as compared to unaffected dogs. We thus performed gel shift assays (EMSA) that reveal that the canine variant significantly alters the binding of regulatory elements. Altogether, these results allowed the identification in dogs of GDNF as a relevant candidate for human HSAN and insensitivity to pain, but also shed light on the regulation of GDNF transcription. Finally, such results allow proposing these sporting dog breeds as natural models for clinical trials with a double benefit for human and veterinary medicine.