title: cGMP-dependent cone photoreceptor degeneration in the cpfl1 mouse retina.
abstract: Inherited retinal degeneration affecting both rod and cone photoreceptors constitutes one of the leading causes of blindness in the developed world. Such degeneration is at present untreatable, and the underlying neurodegenerative mechanisms are unknown, even though certain genetic causes have been established. The rd1 mouse is one of the best characterized animal models for rod photoreceptor degeneration, whereas the cpfl1 mouse is a recently discovered model for cone cell death. Because both animal models are affected by functionally similar mutations in the rod and cone phosphodiesterase 6 genes, respectively, we asked whether the mechanisms of photoreceptor degeneration in these two mouse lines share common pathways. In the present study, we followed the temporal progression of photoreceptor degeneration in the cpfl1 retina, correlated it with specific metabolic markers, and compared it with the wild-type and the rd1 situation. Similar to corresponding rd1 observations, cpfl1 cone photoreceptor cell death was associated with an accumulation of cyclic guanosine monophosphate (cGMP), activity of calpains, and phosphorylation of vasodilator-stimulated protein (VASP). Cone degeneration progressed rapidly, with a peak in cell death around postnatal day 24. Furthermore, cpfl1 cone photoreceptor migration during early postnatal development was delayed significantly compared with the corresponding wild-type retina. The finding that rod and cone photoreceptor degeneration was associated with the same metabolic markers suggests that in both cell types similar degenerative mechanisms are active. This raises the possibility that equivalent neuroprotective strategies may be used to prevent both rod and cone photoreceptor degeneration.
authors.affiliation: Division of Experimental Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Tübingen, 72076 Germany.
authors.forename: Dragana
authors.initials: D
authors.lastname: Trifunović
authors.forename: Katja
authors.initials: K
authors.lastname: Dengler
authors.forename: Stylianos
authors.initials: S
authors.lastname: Michalakis
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: François
authors.initials: F
authors.lastname: Paquet-Durand
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000378:metabolism*
chemical_list: D006152:Cyclic GMP