Investigations of Ocular Melanosis in Cairn Terriers

Simon Petersen-Jones, D VetMed PhD DVOphthal DipECVO MRCVS

Aims for our studies

These remain the same as for my previous reports:

1. Completely characterize the disease, Ocular Melanosis, so that we know all the variations of the disease and the range of ages at which dogs can develop the lesions of Ocular Melanosis.
2. Prove beyond doubt the mode of inheritance of Ocular Melanosis.
3. Identify the genetic defect that causes Ocular Melanosis and develop a DNA test for the mutation. Identify the most effective treatment for dogs that do develop the condition.

Progress report

We now have 153 DNA samples from Cairn Terriers either with Ocular Melanosis or closely related to dogs with Ocular Melanosis (OM). We have pedigree information on all of the dogs except for one or two where pedigrees were not available. Our pedigrees have been drawn up into large pedigrees linking affected dogs to help us better analyze the mode of inheritance. We have been able to rule out some modes of inheritance and although we have a theory of the mode of inheritance we are not yet able to prove our theory beyond any doubt. A concerning development in our investigation of the disease phenotype is that we recently have heard of two dogs where a melanoma has developed in an eye with ocular melanosis. This necessitated the removal of the eye - we have seen sections from one of the eyes and been able to confirm the diagnosis. One dog appears to have suffered from spread of the tumor from the eye. We have been sent tissues to see if that is the case, these are currently being analyzed. Most ocular melanomas do not spread to other parts of the body so it is of concern that spread occurred in one of the two affected dogs. Obviously it is possible that dogs with Ocular Melanosis can develop other eye problems such as melanomas, the question remains did the melanoma arise because of transformation of the abnormal pigment cells characteristic of Ocular Melanosis? We will need to gather more information before we can decide if an eye with Ocular Melanosis is more at risk of developing a true melanoma compared to an unaffected eye.

We have ruled out the candidate gene GPNMB that we had been investigating. We do not have sufficient funding for a genome-wide scan to map the location of the ocular melanosis gene so we are continuing to look at potential candidate genes. These include genes involved in pigmentation such as the genes encoding tyrosine-related protein 1 and tyrosine-related protein 2. Our strategy is to clone the gene in the dog identify polymorphisms (variations in sequences) that we can use to see if the gene is associated with ocular melanosis. We plan to continue working our way through the candidate genes.