Studies utilizing large animal models of inherited retinal degeneration (IRD) have proven important in not only the development of translational therapeutic approaches, but also in improving our understanding of disease mechanisms. The dog is the predominant species utilized because spontaneous IRD is common in the canine pet population. Cats are also a source of spontaneous IRDs. Other large animal models with spontaneous IRDs include sheep, horses and non-human primates (NHP). The pig has also proven valuable due to the ease in which transgenic animals can be generated and work is ongoing to produce engineered models of other large animal species including NHP. These large animal models offer important advantages over the widely used laboratory rodent models. The globe size and dimensions more closely parallel those of humans and, most importantly, they have a retinal region of high cone density and denser photoreceptor packing for high acuity vision. Laboratory rodents lack such a retinal region and, as macular disease is a critical cause for vision loss in humans, having a comparable retinal region in model species is particularly important. This review will discuss several large animal models which have been used to study disease mechanisms relevant for the equivalent human IRD.

Progressive vision loss, caused by retinal degenerative (RD) diseases such as age-related macular degeneration (AMD), retinitis pigmentosa (RP) and Leber congenital amaurosis severely impacts quality of life and affects millions of people. Finding efficient treatment for blinding diseases is among the greatest unmet clinical needs. The evagination of optic vesicles from developing pluripotent stem cell-derived-neuroepithelium and self-organization, lamination and differentiation of retinal tissue in a dish generated considerable optimism for developing innovative approaches for treating RD diseases, which previously were not feasible. Retinal organoids may be a limitless source of multipotential retinal progenitors, photoreceptors and the whole retinal tissue, which are productive approaches for developing RD disease therapies. In this study we compared the distribution and expression level of molecular markers (genetic and epigenetic) in human fetal retina (age 8-16 week) and human embryonic stem cell (hESC)-derived retinal tissue (organoids) by immunohistochemistry, RNA-seq, flow cytometry and mass-spectrometry (to measure methylated and hydroxymethylated cytosine level), with a focus on photoreceptors to evaluate the clinical application of hESC-retinal tissue for vision restoration. Our results revealed high correlation in gene expression profiles and histological profiles between human fetal retina (age 8-13 weeks) and hESC-derived retinal tissue (10-12 weeks). The transcriptome signature of hESC-derived retinal tissue from retinal organoids maintained for 24 week in culture resembled the transcriptome of human fetal retina of more advanced developmental stages. The histological profiles of 24 wk old hESC-derived retinal tissue displayed mature photoreceptor immunophenotypes and presence of developing inner and outer segments. Collectively, our work highlights the similarity of hESC-derived retinal tissue at early stages of development (10wk), and human fetal retina (age 8-13 wk) and supports the development of regenerative medicine therapies aimed at using tissue from hESC-derived retinal organoids (hESC-retinal implants) for mitigating vision loss.

Ocular melanosis of Cairn terrier dogs is an inherited defect characterized by progressive pigmentation of both eyes which can result in glaucoma and blindness. Pedigree analysis suggests the trait has an autosomal dominant mode of inheritance. We selected 11 potential candidate genes and used an exclusion analysis approach to investigate the likelihood that one of the candidate gene loci contained the Cairn terrier-ocular melanosis locus.

Despite increased recognition of caudal vertebral anomalies in the domestic dog (Canis lupus familiaris), studies describing tail deformities remain limited. To address this gap in the literature, this study aimed to identify and classify the caudal vertebral anomaly phenotypes in a pedigree of Beagles. Subjects included 67 dogs (36 males and 31 females), aged eight months to eight years old (M= 38.8 ± 25.6 months). All 67 dogs were visually examined, and tails were palpated to determine if they had any kinks, bends, misalignments, or deformities in their tail prior to radiographic assessment. Radiographs of the caudal vertebrae were obtained from 53 dogs and evaluated for congenital anomalies, including block vertebrae, hemivertebrae, brachyury (very short tail), and axial deviations. Of the 53 radiographed dogs, 25 (47.2%) exhibited at least one congenital caudal vertebral anomaly, with block vertebrae being the most common finding (43.4%). Four dogs (7.6%) had mild congenital abnormalities detected radiographically that were not identified during physical examination. Based on pedigree structure, an autosomal recessive trait is suspected. These findings demonstrate a high prevalence of caudal vertebral anomalies within this pedigree of Beagles and emphasize the importance of radiographic evaluation for accurate identification and phenotypic classification.