Functional and structural modifications during retinal degeneration in the rd10 mouse

• Published in: Neuroscience Vol. 155; no. 3; pp. 698 - 713
• Main Authors: Barhoum, R., Martínez-Navarrete, G., Corrochano, S., Germain, F., Fernandez-Sanchez, L., de la Rosa, E.J., de la Villa, P., Cuenca, N.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 26.08.2008; Elsevier
• Subjects: Age Factors; Animals; Animals, Newborn; apoptosis; Biological and medical sciences; bipolar cells; Cell Death - drug effects; Cell Death - physiology; cone; Disease Models, Animal; Electroretinography; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Glutamic Acid - pharmacology; In Situ Nick-End Labeling - methods; In Vitro Techniques; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Nerve Tissue Proteins - metabolism; Neurology; phosphodiesterase; retina; Retina - drug effects; Retina - metabolism; Retina - pathology; Retina - physiopathology; Retinal Cone Photoreceptor Cells - pathology; Retinal Degeneration - genetics; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal Degeneration - physiopathology; Retinal Rod Photoreceptor Cells - pathology; rod; Time Factors; Vertebrates: nervous system and sense organs; RCS; IPL; rod; bipolar cells; apoptosis; cone; P; retina; phosphodiesterase; ERG; mGluR6; RP; β-PDE; β subunit of the cGMP phosphodiesterase; Royal College of Surgeons; inner plexiform layer; metabotropic glutamate receptor 6; electroretinogram; retinitis pigmentosa; postnatal day; Cone; Bipolar neuron; Rod; Rodentia; Retina; Eye; Visual system; Vertebrata; Mammalia; Mouse; Cell death; Animal; Degeneration; Apoptosis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.06.042

Mouse models of retinal degeneration are useful tools to study therapeutic approaches for patients affected by hereditary retinal dystrophies. We have studied degeneration in the rd10 mice both by immunocytochemistry and TUNEL-labeling of retinal cells, and through electrophysiological recordings. The cell degeneration in the retina of rd10 mice produced appreciable morphological changes in rod and cone cells by P20. Retinal cell death is clearly observed in the central retina and it peaked at P25 when there were 800 TUNEL-positive cells per mm 2. In the central retina, only one row of photoreceptors remained in the outer nuclear layer by P40 and there was a remarkable deterioration of bipolar cell dendrites postsynaptic to photoreceptors. The axon terminals of bipolar cells also underwent atrophy and the inner retina was subject to further changes, including a reduction and disorganization of AII amacrine cell population. Glutamate sensitivity was tested in rod bipolar cells with the single cell patch-clamp technique in slice preparations, although at P60 no significant differences were observed with age-matched controls. Thus, we conclude that rod and cone degeneration in the rd10 mouse model is followed by deterioration of their postsynaptic cells and the cells in the inner retina. However, the functional preservation of receptors for photoreceptor transmission in bipolar cells may open new therapeutic possibilities.