Goniodysgenesis and glaucoma in Border Collies

Due to abnormal development of intraocular fluid egress channels inside the eye the iridocorneal angle, through which the excessive chamber fluid is filtered and drained, get narrower or closed. The primary glaucoma or glaukoma is a painful eye disease that is often associated with elevated intraocular pressure. This increased pressure within the eye damages the ganglion layer of retina and leads to blindness.

This disease was first observed in Border Collies in Australia in the late 1990s and has subsequently been found in Europe and the USA, mainly in dogs related to the affected Australian dogs. Recently, many dogs in the USA become affected with severe goniodysgenesis and glaucoma. Besides Border Collies, the disease also affects other breeds such as Flat Coated Retriever, Springer Spaniel, Cocker Spaniel, and Basset hound, Golden Retriever or Leonberger.

Goniodysgenesis occurs in two forms – severe and mild. Predisposition to the severe form of this disease is caused in most Border Collies by the mutation in the gene encoding for olfactomedin-like 3 (OLFML3). This encoded protein facilitates protein-protein interactions, cell adhesion and intracellular interactions and has a general supporting function. During creation of this protein, the missense mutation c.590G>A (p.Arg197Gln) changes arginine to glutamine which causes changing of its effects and properties. It seems that the mild form of the disease is not associated with this mutation and can be caused by other genetic predispositions.

The mutation p.Arg197Gln is in many cases responsible for severe goniodysgenesis, a prerequisite for primary glaucoma in homozygous dogs. The phenotypes of homozygotes and heterozygotes are very variable. In some heterozygotes, affected phenotypes occur (even without glaucoma), but some heterozygotes remain clinically unaffected.  This indicates that there are some modifiers that can compensate the mutation on OLFML3 or again prevent its compensation.

Severe goniodysgenesis potentially leading to glaucoma is connected with homozygosis for A-allele of OLFML3-gene which indicates autosomal recessive mode of inheritance. The vast majority of dogs with severe goniodysgenesis and glaucoma are homozygous for the mutation mentioned, however there are some cases of heterozygotes affected with this disease. The exact mode of inheritance has not been elucidated yet.

In some dogs, the glaucoma has not been diagnosed although suffering from severe goniodysgenesis. This finding indicates that it is essential for glaucoma occurrence; however for the progress of severe goniodysgenesis to glaucoma a combination of other genetic, environmental or random factors supporting its development is needed.

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Reference:

Carys A Pugh, Lindsay L Farrell, Ailsa J Carlisle, Stephen J Bush, Violeta Trejo-Reveles, Oswald Matika, Arne de Kloet, Caitlin Walsh, Stephen C Bishop, James GD Prendergast, Jeffrey J Schoenebeck, Joe Rainger, Kim M Summers: Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed. doi: https://doi.org/10.1101/321406