Dominant Progressive Retinal Atrophy (D-PRA)
Dominant Progressive Retinal Atrophy (D-PRA) is an eye disorder, which belongs in progressive retinal atrophy group of disorders, known as PRA. This group of disorders comprises inherited diseases that lead to degeneration of retinal photoreceptor cells in dogs and other pets. In general, these diseases are characterized by poor dark vision, visual field defects, and abnormalities in the electroretinogram. PRA is progressive and easily leads to blindness. It appears in both eyes simultaneously. The age of onset and rate of retinal degeneration varies between the different forms of the conditions. Some forms of PRA are common to multiple dog breeds, while others are recognized in just a single breed. PRA appears in most dog breeds, but also in mixed breed dogs. There are different types of PRA, but the PRA occurring in English mastiffs and Bullmastiffs, differs in its mode of inheritance, it is inherited in an autosomal dominant pattern. Most forms of PRA are inherited in an autosomal recessive manner, with another exception of X-linked PRA.
Retina is a thin tissue localized in the eye that contains photoreceptors, rods and cones. Rods are important for vision in dim light, or also night vision. Rods contain a visual pigment called the rhodopsin, which functions also as a receptor. Rhodopsom is activated by light and a transduction cascade that enables night vision initiated. PRA causes progressive rode degeneration, causing firstly night blindness and with time to full blindness. In dominant PRA, numerous rhodopsin gene mutations have been identified.
Appearance of first symptoms varies, depending on whether is the dog homozygous or heterozygous. Dogs homozygous for D-PRA mutation develop symptoms already at 3 months of age, while heterozygous start to show same symptoms by 13 months of age, when ERG results show abnormal rode and cone photoresponses. Usually by the 1 or 2 years of age, affected dogs develop complete blindness. There have been also cases reported where D-PRA affected dogs did not show any symptoms until the age of 7.
Dominant Progressive Retinal Atrophy (D-PRA) is caused by point mutation p.Thr4Arg in RHO gene. It is inherited as a autosomal dominant disorder. This means that one copy of mutated gene is enough for dog to develope the symptoms of PRA.
There has not been developed a cure for PRA. Since in some dogs symptoms of D-PRA do not occur until few years of age (in some cases up to 7 years of age), it is important to be able to recognize dog possessing the defected gene prior to breeding. The only way to detect mutated genes is to do genetic testing.
Kijas JW, et al (2002.): Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa .Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6328-33.