Comparison of ocular RNA profiles of dogs with healthy eyes versus those with primary closed angle glaucoma

Primary glaucoma is a painful and blinding disease associated with pathologically high intraocular pressure. Primary glaucoma affects over 40 breeds of dogs worldwide and at least 1500 dogs in the UK each year. Treatment is usually unsuccessful and most affected dogs ultimately require removal of their eyes on welfare grounds. The most common form of canine primary glaucoma is primary closed angle glaucoma which has been shown to be significantly associated with pectinate ligament dysplasia, an abnormality affecting the iridocorneal angle. Primary closed angle glaucoma and pectinate ligament dysplasia are prevalent in several breeds in the UK including the Flatcoated Retriever, Dandie Dinmont Terrier, Basset Hound and Welsh Springer Spaniel. We have recently reported PLD prevalence in all four of these breeds. With the aid of a previous ECVO grant, we have also performed Genome Wide Association Studies in these four breeds. Prioritisation and validation of candidate variants from identified associated regions would be greatly facilitated by gene expression profiling of clinically relevant tissues.  We have extracted RNA from the iridocorneal angle tissues of dogs with normal/healthy eyes (n = 4) and those with primary closed angle glaucoma (n = 8). We will perform ribosomal RNA depletion on these RNA samples followed by next-generation sequencing, and compare RNA expression levels between eyes affected by primary closed angle glaucoma and healthy control eyes. To our knowledge this study is the first to investigate RNA expression in the iridocorneal angle of both normal canine eyes and those affected by primary closed angle glaucoma. The data will aid in the identification of candidate causal variants for primary closed angle glaucoma. This project will dramatically assist in our long-term aim of developing DNA tests for primary closed angle glaucoma in multiple breeds.