Introduction

• Group of diseases with similar clinical signs but with different underlying genetic causes depending on breed.
• Cause: hereditary (most types are autosomal recessive in inheritance, but X-linked and dominant forms reported in some breeds).
• Signs:
  • Initial night blindness progressing to total loss of vision over a period of months or years.
  • Bilaterally symmetric tapetal hyper-reflectivity, blood vessel attentuation, optic disk pallor, loss of pigment in non-tapetal fundus.
  • Secondary cataract may develop.
• Diagnosis:
  • Characteristic bilaterally symmetric fundus lesions in a dog of typical breed and age, with history of night blindness preceding day blindness.
  • DNA tests from blood and/or cheek swabs are available in a number of breeds - see website links for current list of tests available.
• Treatment: none possible at present. Gene therapy possible in the future.
• Prognosis: blindness and possible cataract formation.
  Print off the owner factsheet Progressive retinal atrophy (PRA) Progressive retinal atrophy (PRA) to give to your client.

Pathogenesis

Etiology

• Inherited, usually as autosomal recessive trait.
• X-linked described in Siberian Husky.
• Autosomal dominant described in Mastiff breeds.

Predisposing factors

• Breed.

Pathophysiology

• An inherited genetic defect leading to abnormal gene expression within the retina (usually within the rod photoreceptors, but in some breeds the primary defect may be elsewhere, eg in cone photoreceptors in the miniature long-haired dachshund).
• This leads to subsequent dysfunction of an important photoreceptor protein and dysplasia or degeneration of rod and cone photoreceptors.
  Either Dysplasia(photoreceptors affected before retina reaches maturity at about 6 weeks of age).
  Or Degeneration(photoreceptors affected after retina reaches maturity at about 6 weeks of age).
• Vision impaired.

Example: Rod-cone dysplasia-1 (rcd-1) in the Irish Setter

• Abnormality in the beta subunit of cyclic guanosine monophosphate (cGMP)-phophodiesterase (one of the components of the visual transduction cascade) → decreased degradation of cGMP → increased levels of cGMP → toxic changes in photoreceptor outer segments (particularly rods) → destruction of photoreceptor outer segments → visual deficits → electroretinographically detectable reduced photoreceptor function → loss of outer (and later the inner) layers of retina → ophthalmoscopically detectable retinal thinning (tapetal hyper-reflectivity and loss of pigment in non-tapetal fundus) → blood vessels attenuation → optic nerve pallor atrophy.

Timecourse

• Dysplasias tend to progress more rapidly than degenerations (except in Miniature Schnauzer).

• Irish Setter may be night blind by 3 weeks old and totally blind by 1 year old.
• Miniature Schnauzer: dysplasia detectable from 8 weeks old (electroretinogram) and from 1 year old (ophthalmoscope) but does not go blind until 4-6 years old.

• Miniature Poodle, Cocker Spaniel and Labrador Retriever tend to develop at 3-5 years old or older. Early form is also seen in Labradors.
• The earlier an animal is affected, the quicker the disease progression.

Diagnosis

Treatment

Prevention

Outcomes