Primary open angle glaucoma in Beagles (POAG)

 

Glaucoma is a heterogeneous group of disorders that lead to blindness due to the death of retinal ganglion cells and damage to the optic nerve. It is the most common cause of the blindness and visual impairment in humans and dogs worldwide (Bouhenni et al., 2012). In general, the glaucoma is classified as primary (in most cases inherited) and secondary (acquired due to eye damage - e.g. injury, tumour and others) (Kotman et al., 2003).

The primary glaucoma is sub-divided in three groups by the iridocorneal angle (the angle between the iris, the cornea and the white):

  • Primary open angle glaucoma (POAG)
  • Primary angle closure glaucoma (PACG)
  • Primary congenital glaucoma (PCG)

In Beagles, the glaucoma of POAG and PACG types may occur. The PACG-type of glaucoma is very rare in dogs and therefore the genotype and the phenotype for this glaucoma type have not been sufficiently studied and no genetic tests are made. The frequency of the POAG-glaucome type occurrence in dog population is higher and has been more often studied and thus genetically tested.

 

The POAG glaucoma is characterized by elevated intraocular pressure (IOP), loss of retinal ganglion cells and atrophy of the optic nerve. (Bouhenni et al., 2012).

 

The clinical symptoms in Beagles occur between 9 and 18 months of age (Kato et al., 2009). They are very different and depend on the duration and rate of disease development and the age of the dog. The main symptoms are:

  • Painful eyes
  • Blepharospasm - lid spasm, squinting
  • Behavioural changes - apathy, loss of appetite,  looking for dark places, depression, aggressive behaviour, eye rubbing 
  • Mydriasis - dilatation of pupil
  • Cornea oedema that causes greyish-blue up to cloudy colour of the cornea 
  • A red (bloodshot) eye - typical for glaucoma
  • Elevated pressure of aqueous fluid 
  • Visual changes, orientation problems 
  • Exophtalmos - protrusion of eyeball from the socket
  • Lens luxation - dislocation of the lens from the normal position
  • Shallow anterior chamber  - narrowing of chamber angle

The success of any glaucoma treatment depends upon how early the condition is diagnosed. The preventive measures include genetic testing (Svoboda et al., 2004).

 

In Beagles, the point mutation c.1981G˃A in ADAMTS10 as a candidate gene on chromosome 20 (CFA20) causing the amino acid substitution p.Gly661Arg has been described as the cause of the POAG-glaucoma (Kuchtey et al., 2013). The protein-coding ADAMTS10 plays an important role in skin, lens and heart development (http://www.ncbi.nlm.nih.gov).

 

Mutation that causes POAG is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P (positive / positive) genotype only. The dogs with P/N (positive /negative) genotype are clinically without any symptom. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.