The Canine Genetics Centre is excited to be resuming its research into primary glaucoma in dogs. This article explains what glaucoma is, and what we are doing to resume our investigations of this painful and blinding canine disease.
What is glaucoma?
Glaucoma is a painful and blinding disease associated with high pressure within the eye that damages the retina & optic nerve resulting in blindness.
In dogs glaucoma is exceedingly difficult to treat, and most affected dogs ultimately require removal of their eyes on welfare grounds, to relieve the excruciating pain that is caused by this disease.
Glaucoma can be secondary to other eye conditions, such as primary lens luxation, inflammation or injury, but If glaucoma occurs in the absence of any preceding eye conditions it is described as primary and is presumed to be inherited.
Primary glaucoma is believed to affect >40 breeds, with an estimated 1500 dogs developing glaucoma in the UK each year.
Dogs suffer from two distinct types of glaucoma – primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG).
In dogs affected with POAG, the drainage angle of the eye (known as the iridocorneal angle or ICA) appears normal, and is usually inherited as a single gene, recessive disease.
In dogs affected with PCAG, the ICA is abnormal. Pectinate ligament abnormality (PLA) is the term given to this abnormality, which can only be detected by a veterinary ophthalmologist, using a technique called gonioscopy. In most breeds investigated to date, PCAG has a complex mode of inheritance, and is not the result of a mutation in a single gene.
Previous research
The Canine Genetics Centre (CGC) has a longstanding interest in inherited eye diseases, including primary glaucoma, and has identified the mutations responsible for POAG in several different breeds, including the Petit Basset Griffon Vendeen [1], the Basset Hound and Basset Fauve de Bretagne [2] and the Shar Pei [3]. The research that led to the development of a DNA test for POAG in the Petit Basset Griffon Vendeen would not have been possible without the remarkable efforts of Peter Bedford, veterinary ophthalmologist, and Vivien Phillips, judge, exhibitor, breeder and all-round force of nature.
Around 2014 the CGC initiated research to investigate the genetics of the more complex form of canine glaucoma, PCAG, in collaboration with the veterinary ophthalmologist James Oliver, who is currently Head of Ophthalmology at DWR veterinary specialists. James was so committed to developing a better understanding of the genetics of this disease that he made it the subject of his PhD thesis, putting endless hours into examining the eyes of hundreds of dogs and collecting their DNA.
This initial work enabled us to estimate the prevalence of PLA in multiple breeds of dog [4-6], and led to some initial genetic findings in the Basset Hound [7].
The CGC’s research into PCAG had to be put on hold following the closure of the AHT in 2020, the CGC’s subsequent move to the University of Cambridge in 2021 and the funding challenges that the CGC was faced with in 2023.
However, that situation has recently changed, thanks in very large part to a large grant that was awarded to the CGC by the trustees of the Jean Lanning Foundation. The grant will fund the continuation of the CGC’s Inherited Eye Disease research, enabling research into PCAG to resume. To start with we will focus on the Basset Hound, a breed for which we have a lot of whole genome sequence data already, and the Welsh Springer Spaniel.
Our aim is to sequence the genomes of 7 PCAG-affected, 10 PLA-affected and 6 Welsh Springer Spaniels with healthy eyes, and undertake a large-scale analysis to compare the genomes of the three groups of dogs and identify genetic variants that underpin the development of PLA and PCAG in this lovely breed.
Over the years we have collected DNA from a lot of PCAG-affected Welsh Springer Spaniels, thanks largely to the tireless efforts of Julie Revill, a previous breed health co-ordinator (BHC) for the Welsh Springer Spaniel and herself the owner of a dog that went blind as a result of glaucoma. Sadly, Julie passed away in May 2023, but is remembered very fondly by the CGC team.
The role of Welsh Springer Spaniel BHC passed from Julie to Arlene Tester, who was a past chairperson of the Welsh Springer Spaniel Club and also a staunch supporter of the CGC’s research. The CGC was saddened to hear of the recent passing of Arlene, in April of this year, and would like to thank her friends and family for making donations to the CGC in Arlene’s memory. At the time of writing over £500 has been donated, all of which will be used to help fund research into PCAG in the Welsh Springer Spaniel.
The CGC will still need additional funds to be able to conduct all the DNA sequencing that we want to do, and we have applied for an additional grant that, if successful, will help cover these costs.
How you can support the Canine Genetics Centre
The Canine Genetics Centre has received help from many loyal supporters over the years, a few of whom are acknowledged in this article. Donations from our grass-roots supporters will continue to be important to the work that we do, and we appreciate all donations, large and small.
One of the best ways to help support the Canine Genetics Centre is to become a Friend of the CGC, by making a regular donation and allowing us to claim Gift Aid, if appropriate. Regular donations make an enormous difference to our ability to plan our research projects, all of which are aimed at improving the health and welfare of dogs. Could you spare £5 a month and become a Friend of the Canine Genetics Centre?
References
- Forman, O.P., L. Pettitt, A.M. Komaromy, P. Bedford, and C. Mellersh, A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17. PLoS One, 2015. 10(12): p. e0143546 DOI: 10.1371/journal.pone.0143546.
- Oliver, J.A., O.P. Forman, L. Pettitt, and C.S. Mellersh, Two Independent Mutations in ADAMTS17 Are Associated with Primary Open Angle Glaucoma in the Basset Hound and Basset Fauve de Bretagne Breeds of Dog. PLoS One, 2015. 10(10): p. e0140436 DOI: 10.1371/journal.pone.0140436.
- Oliver, J.A., S. Rustidge, L. Pettitt, C.A. Jenkins, F.H.G. Farias, D. Elizabeth A. Giuliano, and B. Cathryn S. Mellersh, PhD, Primary open angle glaucoma/primary lens luxation in the Shar Pei: a candidate gene study reveals a novel mutation in ADAMTS17. American Journal of Veterinary Research, 2017. 79(1): p. 98-106.
- Oliver, J.A., A. Ekiri, and C.S. Mellersh, Prevalence and progression of pectinate ligament dysplasia in the Welsh springer spaniel. J Small Anim Pract, 2016. 57(8): p. 416-21 DOI: 10.1111/jsap.12497.
- Oliver, J.A., A. Ekiri, and C.S. Mellersh, Prevalence of pectinate ligament dysplasia and associations with age, sex and intraocular pressure in the Basset hound, Flatcoated retriever and Dandie Dinmont terrier. Canine Genet Epidemiol, 2016. 3: p. 1 DOI: 10.1186/s40575-016-0033-1.
- Oliver, J.A., A.B. Ekiri, and C.S. Mellersh, Pectinate ligament dysplasia in the Border Collie, Hungarian Vizsla and Golden Retriever. Vet Rec, 2017. 180(11): p. 279 DOI: 10.1136/vr.104121.
- Oliver, J.A.C., S.L. Ricketts, M.H. Kuehn, and C.S. Mellersh, Primary closed angle glaucoma in the Basset Hound: Genetic investigations using genome-wide association and RNA sequencing strategies. Mol Vis, 2019. 25: p. 93-105.
