[Slow retinal degeneration in a mouse model: morphological and functional aspects].
BACKGROUND
Diseases causing sensory impairments are a major clinical and sociological problem, especially those that cause loss of vision, which can significantly decrease the quality of a patient's life. It is therefore necessary to comprehend the mechanisms of the disease and find a treatment which can eliminate its cause. To achieve it, researchers use genetically modified animals for examination, as models of human diseases.


METHODS
In this paper, two animal models of slow retinal degeneration are compared to assess changes in their retinas - mice, homozygous for the PRPH2 gene, and heterozygotes which were obtained by crossing with BALB/c. The degeneration rate was determined by measuring the thickness of particular retinal layers at specific time points. The Flat Mount technique was used to evaluate pigment epithelium deteriora- tion, while electroretinography was used monthly to estimate electrophysiological changes of the retinal photoreceptors in dark and light adaptation.


RESULTS
It was found that the most severe and rapid deterioration was present in homozygotes. It caused a total loss of photoreceptor outer and inner segments, outer nuclear layer and outer plexiform layer. ERG revealed absolute suppression of retinal electrophysiology from the 1st month. Heterozygous mice were less impaired and degeneration progressed more gradually. None of the layers were completely destroyed. Electroretinography revealed progressive loss of retinal activity for the duration of the experiment. In the group of mice manifesting homozygous mutation in the PRPH2 gene, the RPE65 protein expression was abnormal. The cells of these mice were characterized by a lack of cytoplasm continuity and the presence of numerous vacuoles, which may indicate degenerative changes in the pigment epithelium. There were no significant differences in RPE65 protein expression between the control and heterozygous individuals. This may indicate correct cell morphology.


CONCLUSIONS
Each of the tested mouse models of retinal degeneration may find its application in the study of this disease. The differences between them allow the selection of the optimal model for a particular experiment.
Andrzej
A
Sobienieckil
Anna
A
Machalińska
Dorota
D
Rogińska
Irena
I
Baranowska-Bosiacka
Barbara
B
Wiszniewska
Bogusław
B
Machaliński
D000818:Animals; D004195:Disease Models, Animal; D005808:Genes, Recessive; D051379:Mice; D008807:Mice, Inbred BALB C; D009887:Ophthalmoscopy; D064531:Peripherins / Q000235:genetics*; D010641:Phenotype; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
D064531:Peripherins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C578996:Prph2 protein, mouse