25%-30% of RP cases are caused by inherited autosomal dominant (ad) mutations in the rhodopsin (Rho) protein of the retina, which impose a barrier for developing therapeutic treatments for this genetically heterogeneous disorder, as simple gene replacement is not sufficient to overcome dominant disease alleles.
Here, we provide a systematic, morphological and functional analysis of Rho<sup>Tvrm4</sup>/Rho<sup>+</sup> rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations.
The present study aimed to test whether adeno-associated virus (AAV)-mediated delivery of the gene encoding CNTF delays photoreceptor death in the rhodopsin knockout (opsin(-/-)) mouse, an animal model of RP.
We found no evidence for an association between telomere length and the severity of RP as monitored by the cone ERG in patients with the Pro23Hisrhodopsin mutation.
These data indicate that severity of disease correlates with the location of the amino acid residue altered by a rhodopsin mutation in dominant retinitis pigmentosa.
PDE beta is the second member of the phototransduction cascade besides rhodopsin that is absent or altered as a cause of retinitis pigmentosa, suggesting that other members of this pathway may be defective in other forms of this disease.
Further studies of the thermal stability of additional pathogenic rhodopsin mutations in conjunction with clinical studies are expected to provide insight into the molecular mechanism of RP and test the correlation between rhodopsin's thermal stability and RP progression in patients.
More than 100 mutations within the rhodopsin gene have been found to be responsible for some forms of retinitis pigmentosa, a progressive retinal degeneration characterized by night blindness and subsequent disturbance of day vision that may eventually result in total blindness.
This mutation, detected in leukocyte DNA, corresponds to a substitution of leucine for proline in amino acid 347 of the rhodopsin protein, and, therefore, we designated this form of retinitis pigmentosa as rhodopsin, proline-347-leucine.
Adult wild-type (WT) mice and mice carrying rhodopsin deficiency (Rho-/-), a frequently used mouse model of human retinitis pigmentosa, were selected for investigation.
Since the discovery of the first rhodopsin mutation that causes retinitis pigmentosa in 1990, significant progresses have been made in elucidating the pathophysiology of diseases caused by inactivating mutations of G protein-coupled receptors (GPCRs).
Using a model based upon primate data of rod outer segment length and turnover, we have calculated that the delayed phase of the recovery of rod sensitivity in the RP patients tested following strong light adaptation could be due in part to formation of new disc membrane with its normal concentration of rhodopsin rather than in situ regeneration of photopigment.