PDE6ß retinitis pigmentosa

Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterised by progressive loss of the photoreceptors and retinal pigment epithelium, leading to blindness at midlife.

RP may be inherited in an autosomal dominant, autosomal recessive (60% of cases), or X-linked manner. Genetic counselling should be provided to affected individuals and their families once the mode of inheritance has been determined through family history or molecular testing. (Source Orphanet)

RP is the most frequent disease among retinal dystrophies (50%), with no current treatment.

RP prevalence varies from 1/1000 RP (Africa, Oceania, Asia) to 1/4000 in other countries.

 

PDE6ß Retinitis pigmentosa is due to mutations in PDE6B

This retinopathy is one of the most frequent genetic forms of RP.

Rod PDE6 is an enzyme localised in rod outer segments, which plays a key role in the rod phototransduction cascade (process through which light is converted into electrical signals). It is a complex protein composed of two homologous catalytic subunits (PDE6α and PDE6ß) and two copies of an inhibitory subunit (PDE6). PDE6α and PDE6ß subunits are required for rod PDE6 activity.

A dysfunction of the PDE6 protein, and in particular of its PDE6ß – subunit, ultimately leads to rod, then cone photoreceptor, death through apoptosis, and subsequently blindness.

Among retinitis pigmentosa cases, the PDE6B gene is the second most prevalent human locus, after the rhodopsin gene, for which mutations have been found in patients with autosomal recessive RP. PDE6ß mutations account for 4 to 5% of these cases or approximately 140 500 people worldwide.

 

Clinical presentation
of PDE6ß Retinitis pigmentosa

In childhood, affected persons develop night blindness due to rod dysfunction. The peripheral visual field progressively decreases. At around 40 years of age, patients develop peripheral visual field degradation and lose central vision.

At 40 years of age, patients present with symptoms of retinitis pigmentosa that are a constriction of retinal vessels, a pallor of the optic nerve head, pigment deposits in the peripheral retina, a macular atrophy with a preserved perimacular zone and RPE. Generally there is no detectable electroretinogram (ERG) response; a photopic response can occasionally be detected.

normal-retina

Normal Retina

retinitis

Retinitis pigmentosa

From Friedrich Miescher Institute for Biomedical Research