Investigations of a novel retinal disease in Wiltshire sheep : a thesis presented in partial fulfilment of the requirements for the degree of Master of Veterinary Studies in Veterinary Pathology at Massey University, Palmerston North, New Zealand
In 2011 and 2012, nine cases of adult-onset blindness were identified in a single flock of Wiltshire sheep. Affected sheep typically developed detectable night blindness at 2 to 3 years of age, which progressed to complete blindness by 4 to 5 years of age. Opthalmoscopically, the disease was characterised by progressive tapetal hyperreflectivity and attenuation of retinal blood vessels, indicative of retinal thinning and atrophy. Retinal histology revealed a selective loss of rod photoreceptors in the early stages of the disease, with preservation of cone photoreceptors. Secondary loss of cone photoreceptors was seen later in the course of the disease. Retinal degeneration was not accompanied by any other ocular or central nervous system abnormalities. Progressive retinal degeneration targeting rod photoreceptors has not been previously reported in sheep, but this disease has several similarities to inherited retinal dystrophies in other species, particularly progressive retinal atrophy in dogs and retinitis pigmentosa in humans. The disease in sheep is thought to be inherited in either an autosomal dominant or autosomal recessive manner, although additional cases identified recently provide further support for an autosomal dominant mode of inheritance. Initial investigations into the molecular basis of the disease, using a comparative candidate gene approach, did not identify any exonic single nucleotide polymorphisms (SNPs) in the rhodopsin gene of affected sheep that would alter the amino acid sequence. Homozygosity mapping of affected sheep revealed an identical-by-descent region on chromosome 5, but none of the genes within or surrounding this segment were considered to be plausible candidate genes except for GPR98, which is associated with retinitis pigmentosa and sensorineural hearing loss in humans. Investigations into the inheritance and molecular basis of this novel retinal degeneration in Wiltshire sheep are continuing, as this disease may prove to be a useful model for retinal dystrophies in other species, including retinitis pigmentosa in humans.